bluuebunny/crossref_metadata_2025 huggingface dataset:
Suppression of Mitogen‐Induced Lymphoproliferation by Soluble IgG Fc Receptors in Retroplacental Serum in Normal Human Pregnancy
Authors: AARLI Å. , JENSEN T. SKEIE , ULVESTAD E. , MATRE R.
Published: July 2006

A competitive ELISA was used to quantify soluble IgG Fc receptors (FcR) in retroplacental serum (RPS) and peripheral serum (PS) from 10 women after uncomplicated full‐term deliveries. The RPS contained significantly higher amounts of soluble FcR than did PS from the same individuals. RPS suppressed phytohaemagglutinin‐stimulated lymphoproliferation as compared with PS, and a positive correlation (r=0.66) was found between the degree of suppression and the difference in soluble FcR level between RPS and PS. Absorption of sera with Sepharose 4B coupled with heat‐aggregated IgG strongly reduced the immunosuppressive activity, whereas absorption with Sepharose coupled with IgG F(ab′)2 fragments did not. When IgG‐binding material was eluted from Sepharose beads and added to cell cultures, the immunosuppressive activity was restored. The data indicate that soluble FcR at physiological levels have immunosuppressive properties. FcR‐mediated immunosuppression may be of importance for maintenance of local immunosuppression during pregnancy.
Leukaemic T Cells from Patients with Chronic Lymphocytic Leukaemia of T‐Cell Origin Respond to Staphylococcus aureus Enterotoxin Superantigens
Authors: METZGER R. , MELMER G. , SCHONDELMAIER S. , HECKL‐ÖSTREICHER B. , NERL C. , PECHHOLD K. , EPPLEN J. T. , KABELITZ D.
Published: July 2006

We investigated the in vitro responsiveness of peripheral blood lymphocytes from two patients with T‐cell chronic lymphocytic leukaemia (T‐CLL) to Staphylococcus aureus enterotoxin (SE) superantigens. T‐cell receptor (TcR) αβ(Vβ 7.1)‐expressing CD4+ leukaemic T cells from patient HE (white blood cell count 480,000/μl) proliferated in response to SEA and, only at 1000‐fold higher concentrations, to SEB, SED, and SEE. CD4+ CD8+ TcRαβ (Vβ 12.1)‐expressing leukaemic T cells from patient KO (white blood cell count 120,000/μl) were activated by SEB but not by the other tested SEs. In both instances, the activation of leukaemic T cells by SE was dependent on the presence of HLA‐DR+ cells. Southern blot analysis of TcRβ gene rearrangement confirmed that the proliferating cells were derived from the leukaemic T‐cell clone and not from contaminating normal T cells. These data indicate that leukaemic T cells from patients with T‐CLL exert a clonally variable responsiveness to SE superantigens. We conclude that recognition of specific antigen and subsequent signal transduction can be initiated via the TcR of leukaemic T‐CLL cells.
The Alternative Binding Site for Protein A in the Fab Fragment of Immunoglobulins
Authors: IBRAHIM S. , KAARTINEN M. , SEPPÄLÄ I. , MATOSO‐FERREIRA A. , MÄKELÄ O.
Published: July 2006

Twenty‐six new human or murine monoclonal immunoglobulins (IgM, IgA, murine IgGl or human IgG3) with a known V‐region sequence were tested for alternative (non‐Fc) binding to Staphylococcal protein A. Seven of them did not bind at all. Four immunoglobulins (all mouse IgGl) were bound but easily eluted (at pH 6). They were probably bound via the Fc part. All eleven were classified as negative for alternative binding. Fifteen immunoglobulins were found to bind more firmly; they came off the protein A column at pH 4–3 (alternative binders).

Amino acid sequences of immunoglobulins that have been typed in the present work or earlier (25 binders and 26 non‐binders) were compared. The light chain, the C region of the heavy chain and the D and JH segments look irrelevant for alternative binding. The N‐terminal portion (amino acids 1–94) of the H chain probably forms the ligand of protein A. A peptide making the ligand cannot be reliably localized within this stretch but binder proteins had a high homology in residues 6–29.

All mouse immunoglobulins expressing Vh genes of families J606 or S107 were alternative binders; those expressing other families were non‐binders.
Virological and Immunological Studies in Patients with Acute Viral Hepatitis
Authors: MARCUS S. , AL‐MOSLIH M. , AL‐TAWIL N. G. , KASSIR Z. A.
Published: July 2006

One hundred and seven patients with acute viral hepatitis (AVH) were studied prospectively regarding the viral aetiological agent HAV, HBV and NANB (by exclusion) using radioimmunoassay. Acute HAV infection occurred in 43 patients, and acute HBV infection in 34 patients, while HDS occurred in two patients only. Acute, presumably NANB, infection occurred in 28 patients. Ten out of 28 sera of patients with AHBV infection were positive for smooth muscle antibody by immunofluorescence. Important findings include: (1) presence of delta superinfection in the absence of HBsAg; (2) HBsAg as the only marker in two patients with AHBV infection; (3) concurrent presence of HBsAg and anti‐HBsAg in three patients with AHBV infection.
Structure of the T‐Cell Receptor in a Tiαβ, Tiγδ Double Positive T‐Cell Line
Authors: KUHLMANN J. , GEISLER C.
Published: July 2006

The multichain T‐cell receptor is composed of at least six different polypeptide chains. The clonotypic Ti heterodimer (Tiαβ or Tiγδ) is non‐covalently associated with the CD3 chains (CD3γδɛζ). The exact number of subunits constituting the T‐cell receptor is still not known. It has been suggested that each T‐cell receptor contains two Ti dimers. To gain insight into the structure of the T‐cell receptor we constructed a Tiαβ, Tiγδ double positive T‐cell line which contained four functional Ti chains (Tiαβ, β, γ, and δ). The data demonstrated an absence of Ti dimers containing mixtures of chains other than the typical Tiαβ and Tiγδ combinations. Furthermore, by co‐modulation experiments we demonstrated that the Tiαβ and the Tiγδ dimers were not expressed in the same T‐cell receptor. Our data indicate that the T‐cell receptor does not contain two Ti dimers.
Changes in the Expression of Ig‐Associated Proteins on B Lymphocytes Activated by Anti‐IgM Antibodies
Authors: VOGEL L. , PERSIN C. , HAUSTEIN D.
Published: July 2006

Binding of antigen to receptor complexes on B cells elicits a cascade of intracellular signalling events leading to proliferation and. together with T‐cell help, Ig secretion. Components of the antigen receptor (AgR) complex have been demonstrated to be either covalenlly bound or associated with surface Ig (sIg) molecules. The function of these proteins is still unknown. In order to address this question, we have stimulated B cells with anti‐μ antibodies and have studied possible changes in the expression of AgR complexes. After anti‐μ stimulation, the IgM molecules disappeared rapidly from the cell surface together with the covalently bound proteins. The IgM molecules were internalized and probably degraded. The IgM‐associated heterodimer Ig‐α/Ig‐β was also removed from the cells, leaving the IgD‐associated heterodimer unaffected. Two proteins showed an enhanced association with slg after 15 min and then were gradually removed from the cell surface. Two other proteins became increasingly attached to sIg. This association remained stable for the rest of the culture period (up to 4 h). Further studies are underway to characterize these proteins more closely and to examine possible interactions with downstream members of the signalling cascade.
Adhesion Molecules Involved in Protein Kinase A‐ and C‐Dependent Lymphocyte Adherence to Microvascular Endothelial Cells
Authors: TURUNEN J. P. , USTINOV J. , RENKONEN R.
Published: July 2006

A twofold increase in lymphocyte adherence to rat microvascular endothelial cells (EC) was achieved by incubating EC for 4 h with IL‐1α or dibulyryl‐cAMP (stimulators of protein kinase A, PKA) and PMA (stimulator of protein kinase C, PKC). Monoclonal antibodies anti‐CD11a, anti‐CD18 (LFA‐I) and anti‐CD49d (VLA‐4α) significantly inhibited the increased lymphocyte binding to IL‐lα‐induced EC, anti‐CD 18 and to a lesser extent anti‐CD11a and anti‐CD49d to dibutyryl‐cAMP‐induced EC, whereas only anti‐CD11a and anti‐CD18 monoclonal antibodies inhibited PMA‐induced lymphocyte binding. These findings suggest that stimulation of PK A and PKC induces lymphocyte binding to EC via different adhesion molecules.
Anchorage and Lymphocyte Function: Extracellular Matrix Substrata Control Morphogenesis and Interleukin Production but have Minor Effects on DNA Synthesis
Authors: SUNDQVIST K. G. , PEDARI L. , HAUZENBERGER D.
Published: July 2006

Contact with collagen and fibronectin substrata triggers disruption of aggregates of activated lymphocytes, pseudopodia formation and migration of these lymphocytes onto the substrata. Monoclonal antibodies to the α4 and α5 chains of β1‐integrins inhibit cell substrate adhesion and aggregate disruption on fibronectin substrata. A rat monoclonal antibody to the β1‐integrin chain inhibits lymphocyte adhesion to collagen. Two‐dimensional (2D) and three‐dimensional (3D) collagen substrata have virtually the same capacity to abrogate lymphocyte aggregation. Fibronectin substrata trigger the initial phase(s) of aggregate disruption as effectively as collagen but the later part of the disruption process is relatively incomplete. Serum‐coated plastic does not cause aggregate disruption. These results indicate that disruption of lymphocyte aggregates is a specific event induced via cell surface receptors for extracellular matrix (ECM) components. A major difference between lymphocytes on 2D and 3D extracellular matrix substrata seems to be that the cells detach from the former whereas on the latter infiltration dominates over detachment. Collagen and fibronectin substrata are non‐mitogenic for lymphocytes but they can modulate lymphocyte activation induced by allogeneic cells and Con A. Thus, 3D collagen substrata augment and prolong such induced DNA synthesis, although they slightly delay entry into the S‐phase and decrease IL‐2 production. Collagen substrata, particularly in 3D form, also augment the DNA synthesis of preactivated lymphocytes above the magnitude on serum‐coated plastic. The nature of the substratum determines IL‐1 production. Accordingly, the spontaneous IL‐1 production by mononuclear cells is substantially lower on collagen substrata than on plastic surfaces coated with serum or BSA. However, factors which induce IL‐1 production (e.g. Con A or LPS) are more effective on collagen than on serum‐coated plastic.

Abrogation of cell aggregation, induction of morphogenesis and motile behaviour as well as control of IL‐1 synthesis thus constitute major effects of ECM substrata on cells of the immune system. An additional but relatively minor influence of ECM substrata on these cells, as suggested by the present results, is exerted via modulation of DNA synthesis.
Human B Lymphocyte In Vitro Response to the Group B Streptococcal Type III Capsular Carbohydrate
Authors: FELDMAN R. G. , RIJKERS G. T. , ZEGERS B. J. M.
Published: July 2006

Anti‐group B streptococcal type III polysaccharide‐specific human B cells from the peripheral circulation can be activated and delected in an in vitro culture system. It is possible to detect both IgM‐ and IgG‐producing cells from both seropositive and seronegative donors. The specificity of the response was demonstrated by inhibition with excess liquid phase antigen and the use of related but antigenically distinct control antigens. The response was absent without the addition of T cells, optimal at 10% and 25% T cells respectively for IgM‐ and IgG‐secreting cells, and undetectable using 50% T cells. The optimal antigen concentration for in vitro B‐cell activation is 2.5 × 10−4μ/ml. Cells from 5 of 6 seropositive donors and 3 of 7 seronegative donors produced specific IgM antibody after culture with antigen. We conclude that the control of the human antibody response to the group B streptococcal type III polysaccharide is influenced by T cells. The response seen in the culture system may be of value in assessing future vaccine candidates designed to prevent neonatal infections.
T Cells Recognizing Multiple Peptides of Myelin Basic Protein are Found in Blood and Enriched in Cerebrospinal Fluid in Optic Neuritis and Multiple Sclerosis
Authors: SÖDERSTRÖM M. , LINK H. , SUN J.‐B. , FREDRIKSON S. , KOSTULAS V. , HÖJEBERG B. , LI B.‐L. , OLSSON T.
Published: July 2006

The cause of multiple sclerosis (MS) is unknown. Recently reported abnormal T‐cell responses to several myelin proteins and myelin basic protein (MBP) peptides in peripheral blood constitute one line of evidence that autoimmune mechanisms could be involved in the pathogenesis of the disease. Monosymptomatic unilateral optic neuritis (ON) is a common first manifestation of MS and important to examine for a possible restriction of the T‐cell repertoire early in the disease. T‐cell activities to MBP and the MBP amino acid sequences 63–88, 110–128 and 148–165 were examined by short‐term cultures of mononuclear cells from cerebrospinal fluid (CSF) and blood in the presence of these antigens, and subsequent detection and counting of antigen‐specific T cells that responded by interferon‐gamma (IFN‐γ) secretion. Most patients with MS and ON had MBP and MBP peptide‐reactive T cells in CSF, amounting to mean values of between about 1 per 2000 and 1 per 7000 CSF cells and without immunodominance for any of the peptides. Numbers were 10‐fold to 100‐fold lower in the patients′ blood. Values were similar in ON and MS, and no evidence was obtained for a more restricted T‐cell repertoire in ON. The MBP peptide‐recognizing T‐cell repertoire was different in CSF than in blood in individual patients with ON and MS, thereby giving further evidence for an autonomy of the autoimmune T‐cell response in the CSF compartment. No relations were observed between numbers of autoreactive T cells and presence of oligoclonal IgG bands in CSF or abnormalities on magnetic resonance imaging of the brain in ON or clinical variables of MS. The high numbers of MBP and MBP peptide‐reactive T cells could play a role in the pathogenesis of ON via secretion of effector molecules, one of them being IFN‐γ, as well as in the transfer of ON to MS.
Transient Depletion of T Cells with Bright CD11a/CD18 Expression from Peripheral Circulation during Acute Kawasaki Disease
Authors: FURUKAWA S. , MATSUBARA T. , TSUJI K. , OKUMURA K. , YABUTA K.
Published: July 2006

To clarify the activation of peripheral blood T cells in Kawasaki disease (KD) patients, we investigated whether expression of lymphocyte function‐associated antigen‐1 (LFA‐1, CD11a/CD18) and/or intercellular adhesion molecule‐1 (ICAM‐1, CDS4) on peripheral blood T cells increases during the acute stage. Expression of cellular adhesion molecules was measured using flow cytometry. There was a decrease in the percentage of CD3+ T cells in the bright LFA‐1α and LFA‐1β population and a concomitant increase in the dim population of LFA‐1α and LFA‐1β during the acute stage, in comparison with those of the convalescent stage. In addition, we observed no significant differences in ICAM‐1 expression during the acute stage compared with that of the convalescent stage. In our view the present data, in conjunction with previous reports on T‐cell function during acute KD, suggest that activated T cells are temporarily withdrawn from peripheral circulation during acute KD.
Common Peptide Epitope in Mumps Virus Nucleocapsid Protein and MHC Class II‐Associated Invariant Chain
Authors: HYÖTY H. , PARKKONEN P. , RODE M. , BAKKE O. , LEINIKKl P.
Published: July 2006

The present study describes a 7 amino acid‐long sequence (YQQQGRL) which is identical in HLA‐associated invariant chain and mumps virus nucleocapsid protein and is additionally followed by one conservative amino acid pair. As such a long amino acid homology is extremely rare in two evolutionarily unrelated proteins the possibility that it could induce immunological cross‐reactivity was evaluated. Several antigenicity indices suggested high antigenic potential within this region. Synthetic peptides containing this sequence were reactive with 31% of monoclonal antibodies specific for mumps virus nucleocapsid protein in ELISA. High antibody levels against this epitope were found in 7% of mumps‐seropositive human sera and antibody levels clearly increased after natural mumps infections and mumps vaccinations. Rabbit antibodies raised against a synthetic invariant chain peptide AYF‐LYQQQGRLDKL‐C reacted with corresponding nucleocapsid peptide RFAKYQQQGRLEAR‐C and antibodies against the nucleocapsid peptide reacted with the invariant chain peptide. Rabbit antibodies against the invariant chain peptide also reacted with nucleocapsid molecules in formaldehyde‐fixed mumps virus‐infected cells, and antibodies against the nucleocapsid peptide reacted with invarianl chains expressed in methanol‐fixed cells. One monoclonal antibody specific for the nucleocapsid molecule also reacted with cells expressing invariant chains. In immunoprecipitation rabbit antibodies against the invariant chain peptide bound to invariant chains while antibodies against the nucleocapsid peptide did not. The results suggest tha t there is antigenic similarity in mumps virus nucleocapsid molecule and HLA‐associated invariant chain which may cause immunological cross‐reactivity between these molecules.
Organ‐Specific Regulation of Interferon‐γ, Interleukin‐2 and Interleukin‐2 Receptor during Murine Infection with Trypanosoma cruzi
Authors: ROTTENBERG M. E. , SUNNEMARK D. , LEANDERSSON T. , ÖRN A.
Published: July 2006

We have studied the expression of IFN‐γ, IL‐2 and IL‐2 receptor (IL‐2R) at the mRNA and protein levels in spleen and lymph node cells from Trypanosoma crizi‐infected BALB/c mice. At 21 days post infection (dpi) (peak of parasitaemia), spleen cells stimulated with Con A for 16 h showed a reduced IFN‐γ, IL‐2 and IL‐2R mRNA production compared with non‐infected controls. Lymph node cells obtained at 4, 21 or 60 dpi produced similar amounts of IFN‐γ, IL‐2 or IL‐2R transcripts after mitogen stimulation as uninfected controls.

Spleen cells obtained at 21 dpi showed a lower Con A proliferative response and IL‐2R expression compared with non‐infected controls, while the proliferation and IL‐2R expression of lymph node cells at 21 dpi was unaltered. Supernatantsfrom 48 h Con A‐stimulated spleen and lymph node cells from mice at 21 dpi had very low levels of IL‐2 but contained significantly higher levels of IFN‐γ compared with the supernatants of cells from non‐infected mice. The latter phenomenon correlates with an accelerated rate of IFN‐γ mRNA accumulation.
CD1 1b/CD18‐Dependent Polymorphonuclear Leucocyte Interaction with Matrix Proteins in Adhesion and Migration
Authors: LUNDGREN‐ÅKERLUND E. , OLOFSSON A. M. , BERGER E. , ARFORS K.‐E.
Published: July 2006

Adhesion of human polymorphonuclear leucocytes (PMN) stimulated with phorbol myristate acetate (PMA) to plastic dishes coated with the matrix proteins laminin (LM), libronectin (FN), collagen type I (CI) or collagen type IV (CIV) was inhibited by the monoclonal antibody 60.3 (MoAb 60.3; anti‐CD18). The highest inhibitory effect was seen on adhesion to CI. PMN adhesion to CI was also effectively inhibited by Mol (anti‐CD11b) but this antibody had only a minor effect on attachment of PMN to the other matrix proteins. In other experiments MoAb 60.3 inhibited LTB4‐induccd migration of PMN through polycarbonate filters (3 μm pores) coated with LM, FN, CI or CIV, with the most pronounced effect on migration through those filters coated with CI. By contrast, the antibody Mol had no effect on migration through any of the protein‐coated filters tested. The results in this study suggest that the CD18 epitope, recognized by 60.3, mediates both adhesion and migration of PMN while theepitopeonCDl 1b recognized by the antibody Mol is restricted to adhesion. The results also indicate that CD11b/CD18 is the major receptor on human PMN for CI while interaction with LM, FN and CIV may in addition involve other mechanisms.
Protective Opsonic Activity of Antibodies against Fibronectin‐Binding Proteins (FnBPs) of Staphylococcus aureus
Authors: ROZALSKA B. , WADSTRÖM T.
Published: July 2006

In this report, opsonic activity of hyperimmune rabbit IgG against fibronectin‐binding proteins (gal‐FnBP A and ZZ‐FnBP B) ofStaphylococcus aureus is described. Moreover, the action of IgG purified from serum of rabbits immunized with ‘combined vaccine’ (fibronectin‐binding protein A + collagen‐binding protein 4‐α‐toxoid) is shown. The opsonic activity has been studied in an in vitro phagocytosis assay as well as in vivo. Mice which had been infected inlraperitoncally with S. aureus strain Cowan l pretreated (opsonized in vitro) with specific anti‐FnBPs IgG were able to eliminate the staphylococci from the peritoneal cavity and liver more rapidly than controls. Also, clearance from the bloodstream of intravenously injected 5. aureus Cowan l as well as S. aureus U320, opsonized with IgG anti‐FnBPs or anti‐FnBP+CnBP +α‐toxoid. was more effective than observed in control groups. In other in vivo experiments it was shown that mice passively immunized with hyperimmune IgG anti‐FnBP (one or two doses, intravenously) before challenge with S. aureus Cov/an l eliminated the bacteria belter than controls injected only with preimmune IgG.
Cytokines and PGE2 Modulate the Phagocytic Function of the β‐Glucan Receptor in Macrophages
Authors: KONOPSKI Z. , SELJELID R. , ESKELAND T.
Published: July 2006

Under serum‐free conditions the β‐glucan receptor of mouse macrophages mediates phagocytosis of β‐l,3‐D‐glucan‐coated microbeads (diameter 2 μm). IFN‐γ increases the phagocytic function of the β‐glucan receptor in a dose‐dependent manner, giving the plateau level at 100 U/ml. Maximum activity appears 9 h after addition of IFN‐γ to the cells. The effect disappears within 24 h. The effect of IFN‐γ may be a result of augmented receptor synthesis since treatment with cycloheximide reduces the phagocytosis.

IL‐1 also increases the phagocytic function of the β‐glucan receptor giving a dose‐dependent response and with the plateau level reached at 10 U/ml. Maximum activity is found 4 h after addition of IL‐I to macrophages. The effect disappears within 24 h. TNF does not alter the phagocytic function of the β‐glucan receptor, but TNF together with IL‐1 prolongs the effect of IL‐1.

PGE2 reduces the phagocytic function of the β‐glucan receptor. Maximum reduction is achieved with 8 ng/ml. Time‐course studies show the lowest phagocytic activity 9 h after addition of PGE2 to the cells.
Aggregated Human Immunoglobulins Bind to Modified Proteins
Authors: LÓPEZ‐BOTE J. P. , LANGA C. , LASTRES P. , RIUS C. , MARQUET A. , RAMOS‐RUIZ R. , BERNABÉU C.
Published: July 2006

Human immunoglobulins treated at 55°C in vitro are able to interact with maleylated bovine serum albumin (mBSA), but not with unmodified BSA. Gel filtration experiments demonstrated that the mBSA binding is associated with a high molecular weight complex of aggregated IgG. This aggregated IgG with binding capacity for mBSA could also be generated in vitro by treatment of human IgG at 37°C or 40°C and by incubation with human neutrophils. Furthermore, IgG aggregates with binding activity for mBSA could be detected in untreated synovial fluids from rheumatoid arthritis patients, indicating that these complexes occur in vivo. The phenomenon of binding to aggregated IgG was extended to other modified proteins such as maleylated human serum albumin (mHSA), acetyl low density lipoprotein (Ac‐LDL) and BSA reacted with oxidized linolenic acid. Soluble forms of these modified proteins were able to compete for the interaction between aggregated IgG and surface‐bound mBSA. We also found that aggregated IgG enhanced the Ac‐LDL‐dependent foam cell formation. These findings suggest a role for aggregated IgG in the metabolism of oxidized proteins.
Oligoclonal Development of Germinal Centre Cells as Detected by Anti‐Idiotype Antibodies
Authors: JONG D. DE , CRAMER G. , BRAND A. , KLUIN P. M.
Published: July 2006

Experimental models using immunization with known haptens have shown that germinal centres develop from only a limited number of precursor cells which expand in an oligoclonal fashion. Using a panel of antibodies raised against the idiotype of follicle centre cell lymphomas and known to be reactive only with a few normal B cells, we could demonstrate that individual clones can be identified within germinal centres of individual follicles of human lymph nodes and tonsils. Therefore also in humans in a non‐experimental, natural situation, germinal centres expand in an oligoclonal fashion.
Peripheral Lymphoid Hyperplasia and Central Lymphoid Depletion in Mice Treated with a Bacterial B‐Cell Mitogen (F3′EP‐Si/p90)
Authors: LIMA M. , PORTNOI D. , BANDEIRA A. , CHAVES M. ARALA
Published: July 2006

In order to further understand the mechanism mediating the mitogenic and immunosuppressor effects of p90, a protein produced by Streptococcus intermedius, flow cytometric studies were performed on peripheral and central lymphoid organs of mice treated with this protein. p90 induced a strong blastogenic B‐cell response in the spleen and lymph nodes, followed by a slight but significant polyclonal T‐cell activation. B‐cell repertoire analysis indicated that polyclonal B‐cell responses affected similarly both CD5+ and conventional (CD5−) B cells in the spleen. Repertoire analysis of T cells failed to reveal any preferential stimulation of the Vβ T‐cell receptor (Vβ‐TcR) families studied. Peripheral lymphoid hyperplasia was observed concomitantly with central lymphoid depiction. In the bone marrow, pre‐B and B cells were profoundly depleted, with a more pronounced effect on small pre‐B cells. In the thymus, double‐positive (CD4+ CD8+) thymocytes were preferentially eliminated, with a relative enrichment of single positive (either CD4+ or CD8+) and double‐negative (CD4−CD8−) thymocytes.
Characteristics of IgA Antibodies Against HIV‐1 in Sera and Saliva from HIV‐Seropositive Individuals in Different Clinical Stages
Authors: MATSUDA S. , OKA S. , HONDA M. , TAKEBE Y. , TAKFMORI T.
Published: July 2006

IgA antibodies were analysed in sera and saliva from 40 HIV‐1 seropositive individuals.

The level of total IgA in serum was elevated according to the progress of the disease. IgA antibodies against p24 and gp160 were detected in the asymptomatic phase of infection. However, they declined in the symptomatic phases in contrast with IgG antibodies. Interestingly, three patients in the symptomatic phase who showed high levels of lgA antibodies were all in relatively good clinical condition. The IgG and IgA antibodies in saliva declined in the symptomatic phase. The level of IgG anti‐p24 antibodies in saliva correlated with that in serum, suggesting that IgG anti‐p24 antibodies in saliva originated from those in the serum. These results indicate that IgA antibodies are regulated independently from IgG antibodies and that the mucosal immune system is impaired early in the symptomatic phase of HIV infection, which starts with mucosal impairment. Detection of IgA antibodies may be useful for prognosis of the disease in HIV‐infected individuals. The results indicate also that treatment for the impaired IgA mucosal immune system should be taken into consideration.
Do Human Peyer's Patches Contribute to the Intestinal Intraepithelial γ/δ T‐Cell Population?
Authors: FARSTAD I. N. , HALSTENSEN T. S. , FAUSA O. , BRANDTZAEG P.
Published: July 2006

T‐cell receptor γ/δ† (TcRγ/γ†) lymphocytes in human Peyer's patches (PP) adjoining ileal mucosa were studied by monoclonal antibodies with paired immunofluorescence staining in situ and by flowcytomelric phenotyping of isolated cells. The proportion of γδ† T cells in the follicle‐associated epithelium outside the M‐cell areas (median 4·I%, range 2·2–30·1%,) was similar to that in mucosal villous epithelium (median 4·4%, range 0·5 30·5%). Most intraepithelial °/δ cells (∼90%) expressed CD45RO but only a few expressed CD8 (<10%) and none l‐selectin; a dominating subset (median 46%) employed the Vδl/JδI gene product (range 22–100%). The M‐cell areas lacked γ/δ cells but contained clustered CD20+ andCD3+ lymphocytes. Thesubepithelial PP dome area and interfollicular(T‐cell) zones, as well as the mucosal lamina propria. contained very few γ/δ cells (median 1·7%, range 0·4–8·9%) which were dominated (88–100%) by the Vγ 2‐encoded subset. Those in the dome area and lamina propria were often (∼75%) CD45RO+ (range 44·90%) while very few (∼2%) expressed i.‐selectin (range 0·15%). By contrast, CD45RO expression on γ/δ cells in the PPT‐cell zones was relatively low (∼46%) and that of l‐selectin relatively high (∼43%). In conclusion, TcR γ/δ+ cells are quite rare in human PP and belong mainly to the Vδ2‐encoded subset, thus being different from most inlraepithelial γδ cells that probably have another origin. The L‐selectin ‘fraction of PPγ/δ cells presumably represent newly recruited ‘naïve’ T lymphocytes while CD45RO+γ/δ cells both in PP and lamina propria arc probably antigen‐primed.
Polyclonal Activation of B‐Lymphocytes and Induction of Autoimmunity in Retrovirus Infected NMRI Mice
Authors: FAXVAAG A. , MOEN T. , DALRN B.
Published: July 2006

Polyclonal activation of B‐lymphocytes accompanies many retroviral infections. Friend derived murine immunosuppressive virus (Fd‐MIV) is a non‐defective murine retrovirus which was isolated from T‐helper cells from mice infected with the acute transforming retrovirus Friend leukaemia complex (FLC). In contrast to FLC, Fd‐MIV does not induce acute transformation of lymphoid and erythroid cells but causes immunosuppression and lymphadenopathy in adult NMRI mice. The effect of Fd‐MIV infection on B‐lymphocytes was studied. Fd‐MIV infection led to a persistent hypergammaglobulinemy with a significant increase in the level of circulating IgG, IgM and immune complexes. In the spleen and lymph nodes, B‐lymphocyte proliferation was found. Parallel to the development of hypergammaglobulinemy, autoantibodies to a variety of nuclear and other autoantigens was detected. In conclusion, the Fd‐MIV infection leads to a B‐lymphocyte dysfunction that has many parallels with AIDS. Furthermore, the Fd‐MIV infection seems to represent an example of an autoimmune condition caused by an exogenous infectious agent.
The Detection and Biological Activity of Human Antibodies to IL‐2 in Normal Donors
Authors: TIBERIO L. , CARUSO A , POZZI A , RIVOLTINI L. , MORELLI D. , MONTI E. , BALSARI A
Published: July 2006

Our study proves that auto‐antibodies to IL‐2 are present also, at a lower litre, in healthy individuals. These antibodies were affinity purified and studied for their capability to interfere with the in vitro biological activity of IL‐2. Data obtained show that human anti‐IL‐2 antibodies can interfere with lymphocyte proliferation both in the lymphokine activated killer (LAK) cell assay and in the mixed lymphocyte reaction (MLR). However, the kinetics of inhibition by anti‐IL‐2 antibodies differs from LAK cell assay to MLR as the former are always inhibited in a time‐independent manner, and the latter only by adding antibodies at the outset of culture. The neutralizing activity observed in vitro suggests that such antibodies play a part in the elaborate cytokine network by which the immune system regulates the amplitude and duration of its response.
Immune Modulatory Effects of Immunoglobulins on Cell‐Mediated Immune Responses In Vitro
Authors: KLAESSON S. , RINGDEN O. , MARKLING L. , REMBERGER M. , LUNDKVIST I.
Published: July 2006

Intravenous Immunoglobulin (IVIG) at a concentration of 5 mg/ml, significantly inhibited mitogenic responses to phytohaemagglutinin (PHA), concanavalin A (conA) and pokeweed mitogen (PWM) by peripheral blood cells from healthy donors. No difference in inhibition by IVIG was seen when stimulating different T‐lymphocyte cell subsets. Inhibition by IVIG was dose‐dependent. An increased response was observed when IVIG was added more than 12 h after PHA compared to adding 1 h before [p= 0·05]. Intravenous immunoglobulin added to mixed lymphocyte cultures (MLC), reduced the median response by more than 60% (range 14–89%; P= 0·03) and almost completely abrogated the lymphocyte response to Staphylococcus aureus protein A (SPA), whose median inhibition was 94% (range 90–99%; P= 0·02).

When comparing 12 different commercial IVIG preparations at a concentration of 2.5 mg/ml, the median inhibition of the PHA stimulation ranged from 4% to 35% and the MLC response from 0% to 66%. In the presence of IVIG the lymphocyte response to different herpes virus antigens was reduced by <50%. No difference in inhibitory effect was seen when comparing IVIG and cytomegalovirus (CMV) hyper Ig, but CMV negative Ig resulted in lower inhibition (P= 0·05].

Three out of five IgG preparations (2.5 mg/ml) made from single donors inhibited PHA stimulation signifiantly more than commercial IVIG [P<0·05]. Mean inhibition was 61% compared to 35% Inhibition by pooled IgG from five donors was 56%. F(ab‘)2 fragments of IVIG inhibited the MLC response by more than 50% (range 34–75%), SPA stimulation by 97% (83–104%) and PHA stimulation by more than 30% (26–37%). One of two Fe preparations tested had an inhibitory effect, but the inhibition was less than that obtained with the F(ab')2 fragments [P= 0.04].

These results further strengthen the notion that IVIG exerts its immune modulatory effect by binding to leukocyte surface receptors. A clear inhibition was obtained with concentrations corresponding to the serum levels obtained when IVIG is given 250–500 mg/kg bodyweight. F(ab')2 fragments have the same inhibitory effect as intact IgG molecules but the role of Fc fragments still remains unclear. Differences in the immunosuppressivc effect of various IVIG preparations may be associated with the method of preparation.
Soluble Intercellular Adhesion Molecule‐1 (ICAM‐1) Antigen in Patients with Rheumatoid Arthritis
Authors: AOKI S. , IMAI K. , YACHI A.
Published: July 2006

Intercellular adhesion molecule‐1 (ICAM‐1), a member of the immunoglobulin supergene family, is known to play an important role in inflammatory diseases. Using a previously developed enzyme‐linked immunosorbent assay (ELISA) with two monoclonal antibodies (MoAbs) against human ICAM‐1, levels of soluble ICAM‐1 (sICAM‐1) were measured in sera from patients with collagen diseases and in synovial fluids (SF) from patients with rheumatoid arthritis (RA). Although the results did not demonstrate that RA and other collagen diseases, as a group, had significantly higher levels of sICAM‐1 in sera as compared with healthy controls, 21 of 138 cases (15%) with collagen diseases and 11 out of 57 patients (19%) with RA clearly showed higher levels of sICAM‐1 in the sera. Comparisons between RA patients of radiological stages I and II and between stage I and other stages showed significantly higher levels of sICAM‐1 in the sera of patients in the latter stages. RA patients with vasculitis and/or pneumonitis showed significantly higher levels of sICAM‐1 than those without vasculitis or pneumonitis. Significant correlations were demonstrated between sICAM‐1 and the factors IgG‐RF, IgM‐RF, erythrocyte sedimentation rate (ESR) and TNF‐α in sera of RA patients. In addition, it was noted that the levels of sICAM‐1 in SF were as high as those in the sera of patients with RA.
Polymorphic Analysis of the Human MHC‐Linked Heat Shock Protein 70 (HSP70‐2) and HSP70‐Hom Genes in Insulin‐Dependent Diabetes Mellitus (IDDM)
Authors: POCIOT F. , RØNNINGEN K. S. , NERUP J.
Published: July 2006

In the present study we characterized the frequencies of two polymorphisms within the MHC‐linked heat shock protein (HSP) 70 genes in patients with insulin‐dependent diabetes mellitus (IDDM) (n= 114) and healthy control individuals (n = 110). Significant differences in genotype and allelic frequencies were observed for both polymorphisms between randomly selected patients and controls. However, for the HSP70‐2 polymorphisms this was solely due to linkage disequilibrium with DR3. The rare HSP70‐Hom 2‐allele was significantly more frequent in controls than in patients. It showed strong association with certain tumour necrosis factor (TNF) (class III) and HLA‐B and ‐A (class I) alleles independent of HLA‐DQ and ‐DR alleles. By typing 257 individuals from 55 IDDM multiple‐case families two extended MHC‐haplotypes, including class II‐, TNF‐ and class I‐markers, carrying the rare HSP70‐Hom allele were defined. One was only transmitted to diabetic offspring, whereas the other was only transmitted to unaffected offspring. The functional implication of the polymorphism in the heat shock‐inducible HSP70‐2 gene was analysed by studying HSP70‐2 mRNA expression after heat shock in peripheral blood mononuclear cells from individuals with different HSP70‐2 genotypes. Preliminary data showed that individuals homozygous for the PstI 8.5‐kb allele consistently had slightly lower expression than heterozygous and 9·0‐kb homozygous individuals.
Immunopharmacologic Modulation of Experimental Allergic Encephalomyelitis: Low‐Dose Cyclosporin‐A Treatment Causes Disease Relapse and Increased Systemic T and B Cell‐Mediated Myelin‐Directed Autoimmunity
Authors: MUSTAFA M. , DIENER P. , SUN J.‐B. , LINK H. , OLSSON T.
Published: July 2006

Therapies with immunosuppressive drugs in autoimmune experimental diseases often down‐regulate disease but sometimes may lead to paradoxical disease exacerbation. To elucidate possible mechanisms behind such phenomena the effects were studied of mitoxantrone (Mx) and cyclosporin A (CsA) given at high and low doses on clinical course, and on autoreactive T‐ and B‐cell responses in actively induced experimental allergic encephalomyelitis (EAE) in Lewis rats. Treatment with mx and high dose CsA abrogated EAE and decreased dramatically the measured immune responses compared to vehicle‐treated control EAE rats. Low‐dose CsA treatment caused a disease relapse 20–30 days post immunization (p.i.). This relapse was accompanied by increased numbers of cells spontaneously producing IFN‐γ in the CNS and regional lymph nodes. Furthermore, anti‐myelin and anti‐MBP secreting cells were increased as were numbers of primed T cells that produced IFN‐γ in response to myelin antigens. It was concluded that these aspects of the myelin autoreactive immune response correlated well with clinical disease and are useful in evaluating immunotherapeutic intervention. Low‐dose CsA treatment may interfere with systemic down‐regulatory mechanisms acting on both T‐ and B‐cell myelin‐directcd autoimmunity.
Commitment to Lymphokine Profile During Primary In Vitro Stimulation
Authors: CARDELL HÖIDÉN S. , MÖLLER G.
Published: July 2006

We have shown previously that different conditions in primary in vitro SEB stimulation of resting CD4+ T cells, could induce selectively production of either IFNγ or IL4 and IL10. The present investigation shows that the priming conditions also decide which lymphokines will be produced during restimulations. The cells that had been induced to produce mainly IFNγ during the primary SEB stimulation, or during stimulation with IL4and ILIO, synthesized the same lymphokines at restimulation, regardless of stimuli and were unaffected by exogenous IL4. Thus, at an early stage of primary SEB stimulation, cells became committed to produce a certain pattern of lymphokines which remained throughout the period of in vitro culture testing.
Phenotypic Characterization of Splenic T Cells from Mice Infected with Plasmodium chabaudi chabaudi
Authors: LANGHORNE J. , PELLS S. , EICHMANN K.
Published: July 2006

T cells from spleens of mice infected with the erythrocytic stages of Plasmodium chabaudi chabaudi have been analysed with respect to their expression of surface molecules CD3, CD4 and CDS and T‐cell receptor (TCR)αβ and γδ. The majority of T cells from infected mice were αβTCR +. However, there was an increase of approximately 8–10‐fold in the proportion and total number of γδ T cells. Immunocytochemical analysis of sections of spleens taken from infected C57BL/6 mice during a primary infection showed that this increase took place particularly in the non‐lymphoid areas. Within the αβ TCR+ T‐cell population, both CD4+ T cells and CD8+ T cells were represented in proportions similar to those observed in normal uninfected mice. Stimulation of splenic T cells from infected mice with P. chabaudi‐infected erythrocytes in vitro resulted ina blasted cell population composed predominantly of αβTTCR+ T cells with no preferential expansion of γβTCR+ T cells. There was no evidence of superantigen‐like stimulation of T cells bearing particular Vβ chains of the TCR. The representation of the different Vβ chains within the population was not significantly different from that seen in uninfected mice.
T‐Cell Stimulation Induced by Idiotypes on Monoclonal Immunoglobulins in Patients with Monoclonal Gammopathies
Authors: YI Q. , BERGENBRANT S. , ÖSTERBORG A. , ÖSBY E. , ÖSTMAN R. , BJÖRKHOLM M. , HOLM G. , LEFVERT A. K.
Published: July 2006

The stimulation of peripheral blood mononuclear cells by purified autologous and/or allogeneic monoclonal IgG was studied in five patients with multiple myeloma (MM), nine patients with monoclonal gammopathy of undetermined significance (MGUS) and six healthy individuals.

Single cells secreting IFN‐γ or IL‐2 were identified using an enzyme‐linked immunospot assay. Patients' cells were preferentially stimulated by autologous monoclonal IgG at low concentrations (1–100 pg/ml). while l00 ng/ml or higher stimulated T cells both from patients and, to a lesser degree, healthy individuals. This biphasic dose‐response of T‐cell stimulation by autologous monoclonal IgG was reproduced in all patients. The numbers of cells secreting IFN‐γ and IL‐2 in response to allogeneic IgG were significantly lower than the numbers obtained using autologous IgG in patients with MM and MGUS. Cells from healthy individuals were stimulated by allogeneic monoclonal IgG, but to a lesser extent.

The results of this study support the presence of idiotype‐reactive T cells in patients with MM and MGUS and also may suggest a general but less pronounced T‐cell reactivity to monoclonal IgG among these patients.
1,25‐Dihydroxyvitamin D3 Exerts Opposing Effects to IL‐4 on MHC Class‐II Antigen Expression, Accessory Activity, and Phagocytosis of Human Monocytes
Authors: XU H. , SORURI A. , GIESELER R. K. H. , PETERS J. H.
Published: July 2006

To investigate the differentiation and activation of monocytes, the combined effects of 1,25‐dihydroxyvitamin D3 (D3) and IL‐4 on human blood monocytes were examined with respect to expression of MHC class‐II antigens, accessory activity, and phagocytic capacity. IL‐4 was reported lo upregulate the expression of MHC class‐II antigens and accessory activity of monocytes. The experiments described here demonstrate that D3 inhibits the expression of all three subtypes of MHC class‐II antigens (HLA‐DR, ‐DP and ‐DQ) as well as the accessory activity of monocytes. both in a dose‐ and time‐dependent manner. However, D3 enhances the immunoglobulin‐ and complement‐dependent phagocytosis by monocytes in a dose‐ and time‐dependent manner. When monocytes are treated with both IL‐4 and D3, the effects of D3 are reverted by IL‐4. suggesting that IL‐4 induces the development of monocytes into accessory cells, whereas D3 stimulates differentiation of monocytes into classical macrophages. These findings provide further evidence for the contention that, depending on defined stimuli, monocytes may develop either into accessory cells or into classical macrophages.
Dermatitis Herpetiformis‐an Autoimmune Disease due to Cross‐Reaction between Dietary Glutenin and Dermal Elastin?
Authors: BÖDVARSSON S. , JÓNSDÓTTIR I. , FREYSDÓTTIR J. , LEONARD J. N. , FRY L. , VALDIMARSSON H.
Published: July 2006

Dermatitis herpetiformis (DH), is associated with skin eruptions and granular depositions of IgA in the papillary dermis, but this is not a feature of coeliac disease (CD). The specificity of the IgA in the skin is unknown. High molecular weight glutenin (HMW‐g), a component of gluten, has been shown to have structural similarities to human elastin. This paper reports immunoadsorption studies which suggest that human serum may contain antibodies which cross‐react with HMW‐g and elastin. DH patients had significantly lower levels of IgA antibodies to HMW‐g and to elastin than both CD patients and healthy controls. Furthermore, introduction of a gluten‐free diet (GFD) was associated with a further reduction in the amount of IgA antibodies to elastin in the DH patients. This diet‐associated decrease of elastin antibodies was restricted to the IgA isotype. A significant correlation was observed between IgA antibodies to HMW‐g and elastin in healthy controls and CD patients, while no such correlation was found in patients with DH. These findings could indicate that HMW‐g induces production of antibodies to elastin, which are deposited in the skin, and that when the antigenic stimulus is removed, these antibodies are further reduced due to continuous dermal deposition. It is postulated that DH may be an autoimmune disease due to cross‐reactivity between dietary glutenin and dermal elastin.
IFN‐γ, IL‐6 and IL‐4 Modulate M. leprae‐ or PPD‐Specific Cytotoxic T Cells in Leprosy Patients
Authors: FINK S. , DE LA BARRERA S. , MINNUCCI F. , VALDEZ R. , BALIÑA L. M. , SASIAIN M. C.
Published: July 2006

Specific cytoloxic T cells against intracellular pathogens may be generated in vitro. On the other hand it is well known that cytokines can regulate almost every aspect of immune function. The aim of this study was to evaluate the effect of some cytokines on the generation of cytotoxic T cells with specificity for Mycobacterium leprae‐ or PPD‐pulsed autologous macrophages from leprosy patients and normal controls. Peripheral blood mononuclear cells from M. bovis BCG‐immunized controls or from leprosy patients were stimulated with antigen, in the presence or absence of cytokines, for 7 days. These were used as effector cells in a 4‐h [5lCr]‐release assay. Our results show that development of cytotoxic T cells may be enhanced by γ‐IFN, IL‐6 or the combination of IL‐6 and IL‐2. Addition of IL‐2 or TNF‐a alone did not modify the generation of cytotoxic activity. IL‐4 down‐regulated the cytotoxic response and γ‐IFN was able to counteract this effect. Hence, the generation of specific cytotoxic T cells can be modulated by cytokines. Whether this cytotoxic mechanism contributes to protection or tissue damage in M. leprae infection remains to be determined.
Okadaic Acid, a Phosphatase Inhibitor, Enhances the Phorbol Ester‐Induced Interleukin‐1B Expression via an AP‐1‐Mediated Mechanism
Authors: HURME M. , MATIKAINEN S.
Published: July 2006

Protein kinase C (PKC)‐activating phorbol esters are known to induce the expression of several genes in monocytic cells. As the effect of serine‐threonine kinases, such as PKC, is often counteracted by specific protein phosphatases, we have now examined the role of phosphatases in the regulation of the phorbol ester (PM A)‐induced interleukin‐B(IL‐1 B) gene expression in theTHP‐1 monocytic leukaemia cell line. Okadaic acid (OA) is a potent tumour promoter, the function of which is based on its activity to inhibit the serine/threonine specific phosphatases 1 and 2A (PPI and PP2A, respectively). Thus, it mimicks or potentiates the action of PKC activators in several cell types. Our data demonstrate that alone OA induced a very weak expression of IL‐B mRNA, but it strongly enhanced the PMA‐induced IL‐1BS expression. To analyse the site of action of OA, the cells were transiently transfected with a chloramphenicol acetyl transferase (CAT) –reporter plasmid containing the AP‐1 binding site as the enhancer. Alone, OA was a weak inducer of CAT–activity in these cells, but again it strongly enhanced the PMA‐induced response. Similar data were obtained with cells transfected with a reporter plasmid containing the PMA‐responsive element (containing a putative AP‐1 binding site) of the IL‐B gene. Thus, these data indicate that the PMA‐induced AP‐1 enhancer activity, which is required for the expression of the IL–lB gene, is controlled in these cells by PPI and/or PP2A. As OA did not synergize with PMA in the induction of expression of genes encoding the AP‐1 proteins (c–fos, c–jun, junB), it is likely that OA potentiates the AP‐1 enhancer activity by its effect on protein phosphorylation.