bluuebunny/crossref_metadata_2025 huggingface dataset:
Complement (C3) Receptor‐Mediated Attachment of Agarose Beads to Mouse Peritoneal Macrophages and Human Monocytes
Authors: JOHNSON E. , BØGWALD J. , ESKELAND T. , SELJELID R.
Published: June 2006

We have determined the receptors on human monocytes and mouse peritoneal macrophages producing agarose binding. By using isolated human complement factors C3, B and D, agarose beads were coated with C3b. In some experiments C3b was converted to C3bi by using human serum diluted 1:20. Agarose beads coated with C3b or C3bi bound strongly to monocytes. Only agarose beads coated with C3bi were attached to mouse macrophages. Trypsinization of agarose beads coated with C3bi abolished the attachment of the beads to macrophages and monocytes, probably because of conversion of C3bi to C3d. Endocytosis by macrophages of agarose preincubated in human serum or in C5‐deficient AKR mouse serum reached the same levels, indicating that the amount of C5 present in serum during preincubation is not important for the degree of endocytosis. It is concluded that internalization of agarose by macrophages is mediated via the C3bi receptor.
The Immune Response to Bacterial Dextrans
Authors: IVARS F. , HOLMBERG D. , COUTINHO A.
Published: June 2006

The in vivo antibody response to the thymus‐independent (TI) antigen dextran B512 (Dex) was studied in various mouse strains. We found no non‐responder strains but rather that the magnitude of Dex‐specific plaque‐forming cell and serum antibody responses varied markedly among individual mice, even if these were of the same age and litter and kept in the same environment. This was the case both for mouse strains previously described genetically as high (IgCHb, j) and for those described as low (IgCHa) responders to Dcx [14]. In‘low’‐responder BALB/c mice, the responsiveness to Dex increased with age, such that a large fraction of these mice responded as well as‘high’‐responder C57BL/6 mice. Analysis of aged back‐cross populations derived from IgCHb and IgCHa parental strains further substantiated these findings. Thus, all backcross mice, irrespective of IgCH haplotype. responded on the average equally well to Dex. According to our studies, therefore, the assignation of high or low responsiveness to IgCH locus‐linked genes cannot be done unequivocally.
Regulation of the Binding of C3‐Coated Particles to Human Lymphocytes by Human Complement Component H*
Authors: FONTAINE M. , DAVEAU M. , GILBERT D.
Published: June 2006

Human complement component H was found to modify greatly the binding of C3‐coated particles to lymphocytes. We used an experimental model in which lymphocytes were mixed successively with various amounts of H and C3b‐coated erythrocytes. At least three mechanisms were postulated to interpret the phenomenon: (i) release of endogenous I by lymphocytes triggered by H through specific binding sites, (ii) cleavage of iC3b by I, promoted by complement receptor type one, and (iii) inhibiiion of immune adherence by H. Such qualitative and quantitative changes in C3‐coated particle recognition by the binding sites might mediate important functions of lymphocytes.
Interferon‐Induced Autologous Reactivity of Human Natural Killer Cells
Authors: TARKKANEN J.
Published: June 2006

The reactivity of human natural killer (NK) cells against normal autologous target cells was studied. The following major observations were made: (i) non‐stimulated NK cells did not lyse autologous target cells, although allogeneic cells were killed to some extent. However, treatment of effector cells with interferon (IFN) resulted in induction of autologous cytotoxicity, and both autologous and allogeneic fibroblast targets were efficiently killed without preference. This was demonstrated both with unfractionated lymphocytes and with effector cells highly enriched in large granular lymphocytes (LGL). (ii) NK cells bound to autologous cells as efficiently as to allogeneic cells. The cells binding to autologous cells were able to lyse K562 cells, demonstrating their NK nature. After stimulation with IFN autologous cells were also killed, (iii) The exemption from autologous cytotoxicity by the non‐stimulated NK cells seemed to result from a block at a post‐binding stage, and there did not appear to be any need for accessory cells in the induction of autologous reactivity by IFN treatment of the LGLs. The results thus point to important post‐binding‐stage regulatory mechanisms saving normal cells from the cytotoxic action of circulating NK cells and may help to understand the suggested role of NK cells in certain autoimmune diseases.
The Migration of Lymphocytes across Specialized Vascular Endothelium VII.
Authors: FOSSUM S. , SMITH M. E. , FORD W. L.
Published: June 2006

The primary migration of lymphocytes from the blood was compared in nude rats and in euthymic rats. The flatter endothelium in the post‐capillary venules (PCV) in the lymph nodes of nude rats was as efficient as the high endotheluim of PCV in euthymic rats at capturing both T and B lymphocytes from the blood, although lymphocytes took a longer time to cross the PCV wall in nude recipients. The organ distribution of both lymphocytes and lymphoblasts ([125I]UdR‐labelled cells) was broadly similar in nude and euthymic recipients. A second aim was to compare B and T lymphocytes with respect to the rate and sites at which they leave the blood after intravenous injection. As judged by sampling venous blood, B lymphocytes left the blood faster, but this was partly attributable to a larger intravascular pool of B lymphocytes in small blood vessels, especially in the lung. Thoracic duct lymphocytes from nude rats collected under standard conditions (16 h, 0°C) entered the cervical lymph nodes very poorly, but when lymphocyte transfer was performed under more physiological conditions entry of B lymphocytes into lymph nodes was about half that of T lymphocytes. B lymphocytes did show a slight preference for entry into Peyer's patches compared with lymph nodes.
Lyt‐Phenotype Conversion of Cytotoxic T Lymphocytes Specific for the A and E Class II Major Histocompatibility Complex Molecules
Authors: VIDOVIC D. , SIMON M.M. , NAGY Z. A. , KLEIN J.
Published: June 2006

The Lyt‐l + (high) Lyt‐2± (low) primary cytotoxic T lymphocytes (CTL) specific for A(AαAβ) molecules and the Lyt‐l +Lyt‐2+ primary E(EαEβ)‐specific CTL are both shown to become Lyt‐l− Lyt‐2 + effector cells after secondary in vitro stimulation. Thus CTL specific for class II major histocompatibility complex molecules exhibit the same Lyt‐phenotype shift as class‐I‐specific CTL do. The data suggest that either both class‐I‐specific and class‐II‐specific CTL follow the same differentiation pathway or regulatory cellular interactions allow only Lyt‐l −Lyt‐2+ cells to differentiate to secondary CTL.
H‐2‐linked Gene(s) Influence the Granulomatous Reaction to Viable Mycobacterium lepraemurium in the Mouse
Authors: CLOSS O. , LØVIK M. , WIGZELL H. , TAYLOR B. A.
Published: June 2006

The genetic control of the granulomatous response to viable Mycobacterium lepraemurium (MLM) was studied in C3H and C57BL/6 inbred strains, BXH recombinant inbred strains, (C3H × C57BL) F1 hybrids, and backcross mice. The results indicate that an autosomal dominant gene, or linked complex of genes, has a marked influence on the footpad reaction to viable MLM. The distribution of responders and non‐responders among 12 BXH recombinant inbred strains and linkage analysis in C3H × (C3H × C57BL)F1 backcross mice indicated that the response gene(s) are linked to the H‐2 complex on chromosome 17. The same gene(s) also influence host restriction of MLM multiplication and thus appear to be the first H‐2‐linked gene(s) influencing resistance to a bacterial infection.
The IgG Subclass Distribution of Thyroglobulin Antibody Synthesized in Culture
Authors: THOMPSON P. M. , McLACHLAN S. M. , PARKES A. , CLARK F. , HOWEL D. , SMITH B. REES
Published: June 2006

Thyroglobulin autoantibodies synthesized by Hashimoto lymphocytes in culture and present in serum have been analysed in terms of their IgG subclass distribution. The autoantibodies produced in vitro were frequently IgG4 or IgG1. whether pokeweed mitogen or Epstein‐Barr virus was used to stimulate the cultures, and the subclass distribution of these thyroglobulin antibodies was similar to that observed in the patients'serum. It appears therefore that the antibodies synthesized in vitro in response to polyclonal B‐cell activators resemble those produced in vivo, and it seems likely that both pokeweed mitogen and Epstein‐Barr virus influence the same B‐cell precursors of autoantibody‐synthesizing celts, albeit by different mechanisms.
Activation of BCL1 Cells by Polyclonal Activators and Inhibition of Growth and IgM Secretion by Anti‐IgM
Authors: SEVERINSON E. , TORRES A. , MOLLER G.
Published: June 2006

Bacterial lipoprotein (LP) and lipopolysaccharide (LPS) both activated an in vitro line of the B‐cell tumour BCL1 to IgM secretion, as determined by the protein A plaque assay. LPS but not LP activation was inhibited by polymyxin B. Activation with both LPS and LP resulted in a less than additive response. Several clones of BCL1 were tested, and all responded to both LPS and LP. Both LPS and LP induced broad dose‐response curves in normal lymphocytes, recently cloned BCL1 cells, and cloned and synchronized (G 1 phase) BCL, cells. This suggests that the dose‐response curve cannot be due to accumulation of responding cells with different threshold sensitivities for activation. We cannot exclude the possibility that the broad dose‐response curve is due to a heterogeneity of the LPS or LP preparation. The results indicate that LPS and LP induce similar signals in BCL, cells. Furthermore, binding to the cell membrane and activation of BCL1 cells by LPS or LP seem to be separate events. An anti‐IgM antiserum inhibited spontaneous DNA synthesis and spontaneous and LP‐induced IgM secretion of BCL, cells. Equal inhibition was observed with F(ab′)2 fragments but not with Fab fragments of the antiserum. suggesting that cross‐linking of IgM bound to the cell surface membrane‐induced inhibition. Supernatants from concanavalin A (Con A)‐activated spleen cells induced BCL1 cells to secrete IgM. Fab anti‐IgM added alone to BCL, cells did not induce IgM secretion. Furthermore. Fab anti‐IgM plus Con A supernatant did not induce a higher response than the supernatant alone. This suggests that inductive signals via the IgM receptor do not occur in BCL, cells.
HLA‐DR3‐ and HLA‐DR7‐Restricted T‐Cell Hyporesponsiveness to Gluten Antigen: A Clue to the Aetiology of Coeliac Disease?
Authors: SCOTT H. , HIRSCHBERG H. , THORSBY E.
Published: June 2006

Coeliac disease (CD) is strongly associated with the human class‐II HLA determinants HLA‐DR3 and ‐DR7. We investigated the relative frequency of gluten‐reactive T cells from DR3‐ or DR7‐positive CD patients and healthy controls who were heterozygous at the DR locus. We found a consistently and significantly lower frequency of gluten‐reactive T cells when the antigen was presented by monocytes in conjunction with DR3 or DR7 than in conjunction with the other DR determinant of the T‐cell donor. In contrast, the frequency of reactive T cells in these donors to other antigens was not reduced in conjunction with DR3 or DR7. These results indicate a specific immunoregulatory function associated with class‐II HLA molecules. The reduced frequency of gluten‐reactive T cells in association with HLA‐DR3 or ‐DR7 may be directly involved in the development of CD.
Characteristics of Chicken Intraembryonic Cells that Express B‐L (Ia‐Like) Antigen under the Influence of Cultured Bursal Epithelium
Authors: EEROLA E. , LASSILA O. , GILMOUR D. G. , TOIVANEN A.
Published: June 2006

In‐vitro‐cultured bursal epithelium (BE) and BE‐conditioned medium (BECM) induce B‐L antigen on chicken intraembryonic cells. Cells prepared from 9‐day‐old intraembryonic mesoderm were fractionated in accordance with cell size by linear albumin gradient sedimentation at 1 g. Two cell types could be distinguished on which expression of the B‐L antigen was altered after a 6‐h incubation with the bursal epithelial component. One fraction contained small mononuclear cells with low sedimentation velocity (≤ 3 mm/h) and low spontaneous proliferation activity. These cells responded strongly to BECM and showed a slight but not significant response to BE (index after incubation with BECM 3.8, with BE 1.7, as compared with RPMI medium control). The other fraction was composed of large mononuclear cells with sedimentation velocity > 9 mm/h and with high spontaneous proliferation. These cells showed a response of equal magnitude to both BE and BECM (index after incubation with BE 2.0, with BECM 2.3). These results suggest that the bursa of Fabricius has influence on two different cell types: a large, probably primitive undifferentiated cell, responding equally to bursal cellular contacts and BE culture supernatant, and a small mononuclear cell type, probably more mature, responding more clearly to the bursal humoral factor.
Evaluation of the Inbred Mouse as a Model for Experimental Treponema pallidum Infection
Authors: FOLDS J. D. , RAUCHBACH A. S. , SHORES E. , SAUNDERS J. M.
Published: June 2006

Mice of several inbred strains were studied for responses to Treponema pallidum (Nichols). Mice were injected with viable treponemes and observed daily for the presence of lesions or signs of illness. Although none of the mice developed detectable lesions, they did develop specific anti‐T. pallidum antibodies that were observed as early as 21 days after inoculation with viable T. pallidum. The antibodies were detected by an enzyme‐linked immunosorbent assay and by passive haemagglutination.
Enrichment of IL‐2‐Producer T Cells from Mouse Spleen by Use of Bauhiniapurpurea Lectin
Authors: IMAI Y. , OSAWA T.
Published: June 2006

Bauhinia purpurea agglutinin (BpA) was used to enrich the interleukin 2 (IL 2)‐producing T‐cell subset from mouse spleen. IL 2 was found to be produced by the BpA‐non‐agglutinated (BpA−) T cells of mouse spleen on stimulation with concanavalin A (Con A). The degree of IL 2 production by BpA‐agglutinated (BpA+) T cells was significamly low. The prolifcrative response to Con A of BpA− T cells was not influenced by the addition of exogenous IL 2, whereas BpA+T cells were partially dependent on the exogenous addition of IL 2 in the proliferative response.
Macrophage Heterogeneity in Thromboplastin Response
Authors: LYBERG T. , AMLIE E. , KAPLUN A. , PRYDZ H.
Published: June 2006

The procoagulant activities of non‐elicited mouse monocytes/macrophages from four anatomical localizations were compared. These cell populations were further examined for their ability to increase their procoagulant activity on exposure to endotoxin or phytohaemagglutinin (PHA). Peritoneal macrophages exhibited the highest basal procoagulant activity. Their activity was further enhanced by stimulation with endotoxin and PHA, but marked strain differences were noted. This procoagulant has been identified as tissue thromboplastin. Isolated adherent spleen cells, peripheral blood monocytes or lung alveolar macrophages had a low basal procoagulant activity that did not increase on exposure to PHA or endotoxin. The identity of the weak procoagulant in these cells is uncertain. The presence of lymphocytes in the macrophage cultures (4:1 ratio) enhanced slightly (1.3 to 1.5‐fold) the response of peritoneal macrophages to endotoxin or PHA but did not significantly influence the procoagulant activity of the other macrophage subpopulations under the conditions tested. These results demonstrate heterogeneity among different macrophage subpopulations with regard to cellular procoagulant expression.
Agar Accumulates in Rat Peritoneal Macrophages Elicited with Thioglycollate Broth
Authors: EICHNER R. D. , SMEATON T. C.
Published: June 2006

Thioglycollate broth‐ and agar‐elicited rat peritoneal cxudate cells contain copious amounts of agar, a sulphated polysaccharide contained in the eliciting agent; the agar content has been measured chemically by the anthrone method for neutral polysaccharides. Adherence experiments confirm that day‐3 thioglycollate‐elicited macrophages coniain 95% of the measured agar; on day 1, 72% is associated with polymorphonuclear cells. Agar ingestion by macrophages coincides with increases in glycogen synthase activity. We suggest that ingestion of agar may be related to the reported deficiencies in function of thioglycollate‐elicited or treated macrophages.
Kinetic Analysis of Subset Growth and B‐Cell Activation in Pokeweed Mitogen‐Stimulated Cultures of Peripheral Blood Mononuclear Cells Depleted of or Enriched for OKT8+ Cells
Authors: JONES B. M.
Published: June 2006

Peripheral blood mononuclcar cells (PBMN) that were depleted of OKT8+ cells and stimulated with pokeweed mitogen (PWM) produced higher cell yields and higher numbers of plaque‐forming cells than unfractionated PBMN. Conversely, OKT8‐enriched PBMN, prepared by mixing unfractionated and OKT8+ cells in a ratio of 3:1, gave reduced cell growth and B‐cell activation. In OKT8‐depleted cultures, B cells, OKT4+ cells, OKT8+ cells, and OKM1+ cells increased in number between days 4 and 7 of culture by factors of 9.8, 5.9, 20.1, and 5.6 respectively, whereas growth rates for these subsets were 2.4, 1.0, 2.0, and 1.3 in unfractionated cultures and 0.9, 1.0, 1.2, and 0.6 in cultures enriched for OKT8+ cells. On day 7 of culture, 73±10% of B cells secreted immunoglobulin in unfractionated cultures, whereas only 21±10% of B cells were activated in OKT8‐enriched cultures. Surprisingly, PWM stimulation of OKT8‐depleted PBMN produced only 40±12% activated B cells.
Chemical Nature of the Interaction between Macrophage Fusion Factor and Macrophage Membranes
Authors: ACOSTA F. A. RODRIGUEZ , GALINDO B. , CESÀRI I. M.
Published: June 2006

Giant‐cell formation induced by macrophage fusion factor (MFF) was not altered after pretreatment of macrophages with trypsin, chymotrypsin, pronase, neuraminidase, phospholipase C, or phospholipase D. Pretreatment of macrophages with either alpha‐mannosidase or alpha‐glucosidase completely inhibited giant‐cell development, without altering macrophage viability. No alteration of giant‐cell formation was observed when 0.1M of L‐fucose, N‐acetyl‐glucosamine, d‐arabinose, d‐xylose, melibiose, d‐glucose, d‐galactose, alpha‐lactose, sucrose, d‐fructose, or maltose was present during incubation of macrophages with MFF. Giant‐cell formation was abolished when 0.1M alpha‐d‐mannose was present during macrophage incubation with MFF. These results suggest that the protein moiety of MFF recognizes a specific receptor site on the macrophage membrane, one that is different from those described for other lymphokines and contains alpha‐mannose.
Anti‐Oxazolone Hybridomas and Strain Distribution of the Oxazolone Idiotype
Authors: McKIMM‐BRESCHKIN J. L. , BRESCHKIN A. M.
Published: June 2006

Antibodies produced in the primary response to the hupten 2‐phenyl oxazolone (OX) express a eruss‐reactive idiotype in BALB/c and DBA/2 mice. We studied the response in hyperimmunized mice, using ascites produced after multiple immunizations with an OX conjugate and by generating monoclonal antibodies. A competitive radioimmunoassay was developed using a rabbit :tnti‐idiotype antiserum raised against purified hyperimmune anti‐OX antibodies, Mice from strains including CBA. C3H/He and B10.BR expressed all the deteminants found in BALB/c serum, although at a lower titre. C57BL/6 mice, however, only expressed some of the BALB/c determinants. We isolated a monoclonal antibody, 1F9, which expressed some of the determinants found in BALB'e serum. All the cross‐reactive idiotopes expressed on 1F9 were also expressed in the above strains including C57BL/6. Almost every BALB/c anti‐OX antibody also expressed the 1F9 determinants. There are thus determinants of the BALB/c OX idiotype which arc expressed in a number of different strains previously thought to be negative for the idiotype.
Lymphocyte Maturation in the Human Thymus
Authors: SCHUURMAN H. J. , VAN LAARHOVEN J. P. R. M. , BROEKHUIZEN R. , SPIERENBURG G. Th. , BREKELMANS P. , FIGDOR C. G. , DE BRUYN Ch. H. M. M. , KATER L.
Published: June 2006

The combination of centrifugal elutriation as an efficient and reproducible method to separate thymocytes by size, micromethods to assess purine interconversion enzymes, and assessment of purine (deoxy) nucleoside inhibition of mitogen responses enabled us to study purine metabolism at the intrathymic level. Out of six fractions, four (nos. 3–6), containing medium‐and large‐sized lymphocytes, showed a proliferative response after stimulation with phytohaemagglutinin (PHA). In fractions 1–6 the number of cells with an immature immunological phenotype gradually decreased, and cells with the phenotype of mature cells gradually increased. The enzyme activity ratio of adenosine deaminase to purine nucleoside phosphorylase gradually decreased from 21 in fraction 1 to 7 in the last fraction (blood T‐cell value, 0.7). We conclude that this enzyme activity ratio is a useful marker for intrathymic T‐cell maturation stages. In PHA‐responsive cell fractions (3–6), the sensitivity to inhibition of the PHA response by (deoxy) adenosine and deoxyguanosine was inversely related to the enzyme activity ratio of ecto‐5′‐nucleotidase to deoxycytidine kinase. These findings are compatible with the hypothesis that intracellular concentrations of phosphorylated (deoxy) nucleosides are related to this inhibition. We conclude that the differences in purine metabolism among the various (mitogen‐responsive) human thymocyte fractions are related to lymphoid cell function. Since the number of cells contributing to the enzyme activities and the number of cells contributing to the proliferative response (about 15% of unseparated cells) differ considerably, it is not possible to evaluate enzyme activities in unseparated thymocytes in terms of relationships between purine metabolism and lymphocyte function.
Inhibition of in Vitro Growth of Plasmodium falciparum by Purified Antimalarial Human IgG Antibodies
Authors: JEPSEN S.
Published: June 2006

In the search for candidate molecules for a malaria vaccine the in vilro inhibition of Plasmodium falciparum cultures by polyclonal or monoclonal antibodies has become a major tool. In the present study antigens identical to antigens circulating in plasma during attacks of malaria have been isolated from supernatants of P. falciparum cultures and used for immunoadsorbent purification of IgG antibodies from a pool of human immune serum collected in Liberia. Approximately 50% growth inhibition of three different P. falciparum isolates from Africa was obtained with the affinity‐purified antibodies at a concentration of 25 μg ml−1 culture medium after 48 h of incubation. The target antigen/antigens for the protective antibodies have been partly characterized by radiolabelling, polyacrylamide gel electrophoresis and autoradiography but have not yet been identified unequivocally. However, the results indicate that one or more of the easily isolated antigens from the supernatant of P. falciparum cultures could be used in a malaria vaccine. The results also indicate that antigenic differences between strains from geographically disparate areas may not constrain the development of such a vaccine.
Complement Receptor Distinguishes between Two Subsets of Large Granular Lymphocytes with Different Natural Killer Activity and Cytochemical and Ultrastructural Features
Authors: NOCERA A. , MONTESORO E. , BALBO P. , FERRARINI M. , LEPRINI A. , ZICCA A. , GROSSI C. E.
Published: June 2006

Human peripheral blood large granular lymphocytes (LGL)—that is, cells with intracytoplasmic azurophilic (electron‐dense) granules, with a positiviiy for the cytochemical localization of certain acid hydrolascs, and with avid surface receptors for the Fc portion of IgG—have been purified on Percoll density gradients. Approximately 30% of these cells expressed receptors for the third complement component (C3R). They were separated into C3R‐positive and C3R‐negative cells. C3R− cells had a significantly greater natural killer (NK) activity against K562 target cells than C3R+ cells. This difference was unrelated to the presence in the C3R+ cells of a contaminant cell type incapable of NK activity, since cytochcmical and ultrastructural analysis revealed that C3R+ and CR− fractions contained comparable LGL numbers. Agarose cytotoxicity assays at the single‐cell level demonstrated that C3R + LGL contained a large number of cells that bound to but did not lyse the target. The remaining fully cytotoxic C3R+ LGL had, however, the same killing and recycling properties as the cells from the OR fraction. Electron microscopy and cytochcmical studies showed that C3R+cells had fewer electron‐dense granules than C3R cells and stained more faintly for the localization of α‐naphtyl acetate eslerase. In contrast to C3R cells. C3R+ LGL displayed morphological features suggesting that an active process of granule formation was taking place. Taken together, the data indicate that C3R+ cells represent a discrete subset or a maturationsl stage of LGL.
Imprint Immunofixation of IgG Subclasses, Using Monoclonal Subclass‐Specific Antibodies
Authors: VARTDAL F. , BIRD P.
Published: June 2006

Monoclonal mouse hybridoma antibodies to human IgG subclasses 1–4 were used in an imprint immunofixation (IIF) technique to characterize the IgG subclass of a panel of IgG myeloma and normal sera separated by thin‐layer electrofocusing. The results show that the antisera were IgG subclass‐specific by this technique and that IIF can be a useful method in identifying IgG subclasses of IgG myeloma proteins in whole sera.
Recovery of Peripheral Lymph Cells from Congenitally Athymic Nude Rats
Authors: TØNNESEN B. E. , FOSSUM S.
Published: June 2006

Thoracic‐duct cannulation of mesenteric lymphadenectomized (MLNx) congenially athymic nude rats was studied as a method of obtaining peripheral lymph cells. A higher recovery of non‐lymphoid cells (NLC) was obtained from nude than from euthmyic littermates. Both a higher percentage and a greater number of NLC were found in nude animals. Most of these cells resembled dendritic or veiled cells and were strongly positive for Ia antigens. This population could further be enriched by irradiation of the animal, but with a risk of cell damage. Splenectomy had no effect on early output of Ia+ NLC. A substantial population of lymphoid cells from MLNx nude rats expressed T‐cell antigens defined by the monoclonal antibodies OX 19, OX 8 or W3/25. These cells were more radiosensitive than were mature T cells. In addition, a large population of cells in the peripheral lymph from nude rats did not display surface antigens recognized by monoclonal antibodies directed either against B cells or against T cells. This cell fraction increased after irradiation. These cells resembled small lymphocytes but had a more irregular nucleus and multiple large granules.
Localization of the Binding Site on IgG for Solubilized Placental Fcγ Receptor
Authors: MATRE R. , TÖNDER O.
Published: June 2006

Placental FcγR (FcR) inhibited the rosette formation between monocytes and rabbit IgG‐sensitized erythrocytes (EA), whereas the rosette formation with granulocytes was not impaired. Staphylococcal protein A (SpA) inhibited the rosette formation with both cell types. Results obtained in absorption and agglutination experiments showed that SpA blocked the binding of FcR to IgG, and C1 did not. Furthermore, FcR did not interfere with the binding of SpA to IgG, whereas C1 affected this binding. FcR apparently bind to the Cγ3 region. Since FcR inhibited the binding of EA to monocytes, the monocyte FcR binding site is probably also located within the Cγ3 region.
In Vitro Effect of Interferon on Development and Function of Bone‐Marrow‐Derived Cytotoxic Diffuse Colonies
Authors: CLAËSSON M.H.
Published: June 2006

The present work shows that addition of mouse beta interferon (IFN) to murine bone marrow cells cultured in the presence of pokeweed mitogen‐spleen‐CM results in an increase in the proportion and number of diffuse colonies. Addition of IFN early in the culture period inhibits the development of the cytotoxic capacity typical for normal diffuse colonies. Addition of IFN late in the culture period, when diffuse colonies have already been formed, enhances the cytotoxic activity of individual colonies. The cellular composition of diffuse colonies was nearly identical in non‐cytotoxic and strongly cytotoxic colonies. It is concluded that IFN profoundly affects development and function of cytotoxic diffuse colonies.
Signal Sequences Distinguish Class II Histocompatibility Antigen ß Chains of Different Loci
Authors: GUSTAFSSON K. , WIMAN K. , LARHAMMAR D. , RASK L. , PETERSON P. A.
Published: June 2006

The signal sequences of two HLA‐DR ß chains and the DR α chain were determined. In addition, the major part of a DC ß‐chain signal sequence was also elucidated. The data were obtained by combining amino acid sequenceanalyses of isolated α and ß chains with nucleotide sequencing of four cDNA clones. All signal sequences comprise 25 amino acids or more. The two HLA‐DR ß‐chain signal sequences are identical and exhibit only marginal homology to the DC ß‐chain signal sequence. No homology is apparent between α‐ and ß‐chain signal sequences. The differences in the signalsequences of the DR and DC ß chains suggest that these sequences may be used to assign ß chains to different loci of the human major histocompatibility complex.
Binding and Activation of the First Complement Component by Soluble Immune Complexes: Effect of Complex Size and Composition
Authors: DOEKES G. , VANES L. A. , DAHA M. R.
Published: June 2006

The interaction between soluble immune complexes and the first component of complement (Cl) was studied. Complexes were prepared from purified bovine thyroglobulin (BTg) or tetanus toxoid (TT) and immunospecific rabbit IgG antibodies. Purified human precursor Cl was incubated with dilutions of the preparations, and the inhibition of Cl haemolytic activity was determined as a measure of Cl‐binding. The activation of Cl was assessed by measuring the amount of C4 consumed by generated Cl. The molar antibody/antigen (Ab/Ag) ratio of BTg‐anti‐BTg mixtures strongly influenced their Cl‐binding and Cl‐activating capacities: mixtures with high Ab/Ag ratios were by far the most efficient. On the other hand, the Ab/Ag ratio had only a limited influence on the activity of TT‐anti‐TT complexes. The effect of complex size was investigated by ultracentrifugation of antibody‐antigen mixtures on calibrated sucrose density gradients followed by Cl‐binding and ‐activation experiments with the fractions obtained. For both types of immune complex, the Cl‐binding and ‐activating capacities increased markedly with increasing complex size. Thus, both the size and the Ab/Ag ratio of soluble immune complexes influence their capacity to activate the classical complement pathway. The effect of the Ab/Ag ratio, however, may also be dependent on the antigen molecule(s) present in the complexes.
Genetic Control of the Murine IgM Plaque‐Forming Cell Response to Type III Pneumococcal Polysaccharide
Authors: PASANEN V. J. , MÄKELÄ O.
Published: June 2006

The direct 5‐day plaque‐forming cell response of different inbred mouse strains to pneumococcal polysaccharide type III (SSS‐III) varied from more than 10,000 per spleen, in BALB/c mice, to less than 2000 in C57BL mice. Responses of Igh congenic and recombinant inbred lines bearing different combinations of BALB/c and C57BL genes indicate that two or more gene loci are involved in controlling high or low responses. At least one is in the Igh‐V region since BALB/c, BAB‐14, and CB‐8 KN mice (Igh‐V2) had two to four times higher responses than CB‐20 and CB‐16 KN mice (Igh‐Vb). Other gene loci must be involved, but nothing can be said about them at present.
Sera from Multiparous Women Contain Antibodies Mediating Cytotoxicity against Breast Carcinoma Cells
Authors: FORSMAN L. M. , JOUPPILA P. I. , ANDERSSON L. C.
Published: June 2006

We have searched for immunological mechanisms contributing to the epidemiologically established phenomenon of lower incidence of breast carcinoma among multiparous women and women with pregnancy at early age. Sera collected from 55 clinically healthy multiparous women were tested for the ability to mediate cytotoxicity in an antibody‐dependent cell‐mediated (ADCC) assay with normal blood leucocytes against three different mammary carcinoma cell lines (MDA‐MB 157, MDA‐MB 231, and MDA‐MB 436), Sera from 12 women (22%) mediated significant cytotysis against all three cell lines. Three additional sera were positive against MDA‐MB 231 and 11) more against MDA‐MB 436 (total 42%). Cross‐adsorptions revealed that the ADCC‐active sera contained antibodies that recognized the same antigen(s) on the different mammary carcinoma‐derived cell lines. The sera from multiparous women contained no detectable ADCC‐active antibodies against a colon carcinoma cell line (SW 1116) or a neurohlastoma cell line (SH‐SY5Y). ADCC‐active antibodies were found neither in sera from 35 nulliparous women nor in sera from 20 men. The ADCC‐active antibodies against mammary carcinoma cells could not he removed by adsorption with lymphoblastoid cells established from the respective husbands of the multiparous women. This observation and the fact that the mammary carcinoma cell lines were established from different patients argue against an impact of HLA‐related antigens. The ADCC‐active antibodies reported here might result from autoimmunization against some proliferation/differentiation antigen(s) of breast epithelium which is (are) expressed during pregnancy and lactation.
Effects of Hydroxyurea on Concanavalin‐A‐Induced T‐Cell Proliferation
Authors: ROCHA B. , LARSSON E.‐L. , FREITAS A A.
Published: June 2006

The effects of eliminating cycling precursors by in vivo administration of high doses of hydroxyurea (HU) in populations of mouse spleen T lymphocytes were studied by membrane immunofluorescence identifying mature Thy 1+, Lyt 2− and Lyt 2+ cell populations and mitogen‐induced T‐cell growth factor (TCGF) production or reactivity to TCGF. HU treatment results in a sharp decrease in the total number of T cells in mouse spleen, indicating that about 50% of peripheral splenic T lymphocytes have a short survival time in vivo. This depletion is more marked for Lyt 2+ cells than for Lyt 2− cells. The decay of TCGF‐reactive spleen cells after drug adminstration is similar to that of the overall spleen T‐cell population. Conversely, production of TCGF induced by concanavalin A is predominantly affected by HU treatment, indicating a shorter life span of the cell(s) involved in TCGF production.
Suppression of Lymphoproliferation and Autoimmunity by Elimination of a Radiosensitive Bone Marrow Cell in Mice Bearing the lpr Gene
Authors: DAUPHINÉE M.J. , TALAL N.
Published: June 2006

The autosomal recessive lpr gene (lymphoproliferative) has been bred into several normal strains of mice. Although the time of disease onset may vary, all of these lpr mice develop hypergammaglobulinaemia, antibodies to nucleoproteins, and massive lymphoproliferation. The abnormalities do not appear in their normal congenic counterparts, which lack the lpr gene. We studied the effects of sublethal whole‐body X‐irradiation (300 rads) on disease features and lymphocyte subpopulations by using flow cytometry. H‐2k strains, C3H and MRL/++ and their autoimmune lpr counterparts, were killed at 1, 2, 4, 8 and 24 weeks after irradiation, which was given at 6–8 weeks of age. In the lpr mice, lymphoproliferation, autoimmunity, mortality and number of Ia+ cells were greatly reduced in the irradiated mice compared with nonirradiated controls. Abnormal cytofluorometric patterns seen with lpr thymocytes were corrected by the low‐dose irradiation treatment. In addition, lethally irradiated lpr mice reconstituted with syngeneic bone marrow from low‐dose irradiated mice exhibited retarded development of autoimmune disease. We conclude that the lymphoid alterations induced by X‐irradiation reflect a recovery of immunologic control associated with suppression of autoimmune manifestations.
Analysis of the Quantity of Antiviral Antibodies from Mink Infected with Different Aleutian Disease Virus Strains
Authors: AASTED B. , TIERNEY G. S. , BLOOM M. E.
Published: June 2006

Mink persistently infected with Aleutian disease virus (ADV) develop hypergammaglobulinaemia and immune complex disease. Radiolabelled antibodies from mink infected with ADV‐G, DK, Pullman, and Utah I strains of ADV were reacted against all four ADV strains in radioimmunoassay (RIA). The amount of anti‐ADV antibody in two equally hypergammaglobulinaemic serum pools varied from 13% (anti‐Pullman) to 57% (anti‐Utah I). Serum pools from two other sources (anti‐DK and anti‐ADV‐G), although less hypergammaglobulinaemic, had 5% and 13%, respectively, indicating that 43–95% of the Ig in the sera of mink with AD was not specific antibody to ADV structural antigens. The possibility of a general polyclonal activation of the humoral immune system is being discussed. Comparison of plateau RIA binding levels for the four serum pools against the four viral antigens suggested three patterns of reactivity: DK and Utah I reacted similarly, but Pullman and ADV‐G reacted serologically different.
Immunohistochemical Localization of Secretory Component in the Liver of Guinea Pigs and Dogs versus Rats, Rabbits, and Mice
Authors: DELACROIX D. L. , FURTADO‐BARREIRA G. , RAHIER J. , DIVE C. , VAERMAN J.‐P.
Published: June 2006

Secretory component (SC) was localized in the liver of guinea pigs, dogs, rabbits, rats, and mice. In rabbits, rats, and mice SC localized predominantly in bile canaliculi and on hepatocyte sinusoidal membranes but was doubtful in cholangincytes. In dogs and guinea pigs SC‐staining was not detected in/on hepatocytes and canaliculi but was strong in/on cholangiocytes, as reported for humans. In guinea pigs IgA biliary output was small (0.23 mg/kg/day), as for dogs and humans, and below IgG output (1.4mg). in contrast to rats, whose IgA biliary output (38 mg/kg/day) was much larger than IgG output (2 mg). Biliary obstruction in guinea pigs induced only minor increases in serum IgA (+ 26% over 24 h), as reported for dogs and humans, in contrast to rats (+ 800% over 24 h) and rabbits. Hepatocyte SC expression correlates with IgA hepatobiliary excretion, being low in guinea pigs, dogs, and humans but high in rats, rabbits, and mice.
On the Molecular Basis of T Helper Cell Function
Authors: RUBIN B. , SUZAN M. , REININGER L. , DENIZOT F. , TAYLOR R. B. , GOLSTEIN P.
Published: June 2006

The differentiation of Ig+ B cells into plaque‐forming cells is dependent on antigen and factors produced by T cells and/or macrophages. We describe here the production of T‐cell factors termed lymphocyte promotor factors (LPF). A foetal calf serum‐specific T‐cell line and its clones synthesize LPF, which is defined as factors that polyclonally stimulate normal spenic T cells to differentiate into cytotoxic T lymphocytes (T‐LPF) and normal splenic B cells to differentiate into plaque‐forming cells into (PFC) (B‐LPF) in the apparent absence of specific antigen. The proliferation of and the B‐LPF production of all T‐cell clones tested were foetal calf serum‐specific and I‐Ab‐restricted. Some of these clones produced only T‐LPF, some clones produced only B‐LPF, and some clones produced both T‐LPF and B‐LPF. B‐LPF stimulate the polyclonal differentiation of Ig+ B cells into PFC without the apparent need for helper T cells, is different from T‐LPF, and induces almost exclusively IgM PFC. The B‐LPF described in the present paper are compared with previously described T‐cell factors, which stimulate antigen‐specific B‐cell responses or bystander B‐cell responses. The conclusion is that B‐LPF are probably different from B‐cell growth factors, T‐cell replacing factors, allogeneic effector factors, and interleukin 2.
Functional and Chemical Characterization of B‐Cell Growth Factor Produced by Normal Cloned T Helper Cells
Authors: PETTERSSON S. , LEANDERSSON T. , FORSGREN S. , POBOR G. , COUTINHO A.
Published: June 2006

Media conditioned by clones of normal helper T cells exposed to appropriate antigenpresenting cells contain growth‐promoting activity for B‐cell blasts induced either by lipopolysaccharide or on direct interaction with competent helper cells. This B‐cell growth factor (TH‐BGApet) is recovered on sodium dodecyl sulphate polyacrylamide gel electrophoresis corresponding to mol. wt of 15,000–20,000 displays no mitogenicity for small, non‐induced B lymphocytes and is completely devoid of the ability to activate immunoglobulin secretion in proliferating B cells. These results are ascribed to the activity derived from normal T cells, with the same characteristics as BSF‐pl previously obtained from lymphomas and hybridomas. Since hybridization of these T helper cells results in the constitutive production of BSF‐pl in the absence of macrophages, these experiments demonstrate that BSF‐pl is a normal T‐cell product.
Thymosin Induces Helper Function in OKT3‐Positive, E‐Rosette‐Negative Human Cord Blood T Cells
Authors: TAN P.L.J. , SHORE A.
Published: June 2006

E‐rosette‐negative lymphocytes (TE‐), which express monoclonal T‐cell markers (OKT3+) were found in higher frequencies in humnn cord blood (CB) (30% by phenotype and 11.7% by sequential rosette isolation) than in adult peripheral blood lymphocytes (13% by phenotype and 3.7% by isolation). TE‐ cells had very low levels of 5′‐nucleotidase. a lymphocyte maturational marker low in thymocytes. Like other CB T cells. TE‐ cells possessed marked suppressor capability. Irradiated TE‐ cells from two cord blood samples demonstrated helper activity tor Ig production hy adult B cells. In six cord blood samples, however, irradiated TE‐ cells lacked helper activity. When incubated with thymosin, these TE‐ cells became E‐ and differentiated into inducer‐helper T cells. These observations confirm previous assumptions that CB T cells are not fully differentiated. Furthermore. T cells from different CB samples may be at various stages of ontogeny. We have also shown that thymosin fraction 5 is able to confer a new immunoregulatory function.
On the Heterologous Interaction between β2‐Microglobulin and the Heavy Chain of Rat Major Histocompatibility Complex Class 1 Antigens
Authors: LÖGDBERG L. , BJÖRCK L.
Published: June 2006

The heterologous interaction between β2‐microglobulin (β2m) and rat major histocompatibility complex (MHC) (RT1) antigens was measured in a two‐step binding assay consisting of binding of radiolabelled β2‐m to RT1 antigens and immunoprecipitation of β2m‐RT1 antigen complexes with RT1 antisera. The effects of varying the concentrations of the three reactants involved were studied. The molecular events taking place in the two steps were analysed by gel chromatography. The β2m‐RT1 antigen complex had the apparent size of albumin and reacted completely with specific alloantisera. RT1 antigens prepared from Wistar/Furth (RT1u) and Brown Norway (RT1n), respectively, both effectively bound heterologous β2m. The times for association and dissociation, respectively, at 37°C, were of the same order, but dissociation was slightly slower. Association was markedly temperature‐dependent and was considerably slower at low temperatures. All these processes were slower for RT1u than for RT1u antigens. The association constant for the interaction between RT1u antigens and 125I‐human β2m was estimated by Scatchard analysis to be about 109 M‐1. Contribution to the heterologous interaction by products from various rat MHC subloci (A, B, and C) was investigated by the introduction of sublocus‐specific antisera in step 2. The reaction apparently involved neither class 2 antigens (sublocus B) nor the presumed rat Qa homologue (sublocus C). Classical class 1 antigens (suhlocus A) clearly contributed to the binding. However, a monoclonal antibody against products from rat MHC class 1 genes only precipitated less than half of the RTI antigen‐complexed β2m. Thus, at least two RT1u class 1 alloantigen molecules seem to participate in the reaction. This, in turn, indicates that the rat genome may contain multiple class 1 genes, an is the case for most other mammals investigated.
Modulation of Pokeweed Mitogen‐Induced Human B‐Cell Differentiation by Aggregated IgG
Authors: BICH‐THUY LÊ THI , REVILLARD J. P.
Published: June 2006

The modulatory effect of human heat‐aggregated IgG on human B‐cell differentiation induced by pokeweed mitogen was investigated with three experimental protocols. Pulse exposure to aggregated IgG, followed by extensive washings before culture, of peripheral blood mononuclear cell suspensions rigorously depleted of platelets and containing less than 4% monocytes resulted in a selective decrease of the numbers of IgG‐containing cells and IgG‐secreting cells, whereas a simultaneous decrease of the numbers of cells producing IgG and, to a lesser extent, of those producing IgM or IgA was observed when the pulsed suspensions contained platelets and more than 4% monocytes. This non‐isotype‐specific suppression was shown to be more pronounced when aggregated IgG and platelets were present in the cell suspensions throughout the cultures. The results suggest that two distinct suppressor pathways can be triggered by aggregated IgG. The first one is restricted to cells producing the matching isotype, in the absence of platelets, with few monocytes in the cell suspensions. The second one leads to a nonspecific suppression of the three major Ig classes. It requires the presence of platelets and/or a high percentage of monocytes and, although it remains to be demonstrated, is probably mediated by prostaglandin E2.
C3 Cleaved by Membrane Proteases Binds to C3b Acceptors Expressed on Concanavalin A‐Stimulated Human Lymphocytes and Enhances Antibody‐Dependent Cellular Cytotoxicity
Authors: ERDEI A. , BHNCZUR M. , FÁBRY Zs. , DIERICH M. P. , GEROELY J.
Published: June 2006

On activation of cells membrane‐associated proteases—including serine esterases known to cleave the third component of complement (C3)—become expressed. In this paper it is shown that as a consequence of this enzyme activity isolated native human C3 added to concanavalin A (Con A)‐activated human lymphocytes is cleaved on the surface of the blast cell. This enables the immediate fixation of nascent C3b (C3bx) through its short‐lived metastable biinliniisite to Oh acceptors (C3bA's) newly expressed on Con A‐stimulaled cells. Aeceptor‐bound C3b is detected by the immune adherence rosette formation of the O‐treated Con A blasts with the C3b receptor (C3bR)‐bearing O. Rh+ erythroeytes (32 ± 4%). The cleavage of C3 and the covalent fixation of C3b are shown to he inhibited hy phenylmethylsulphonyl fluoride and methylamine, respeclively. As a functional consequence of the covalent fixation of C3b to the mitogen‐activatcd lymphocytes it is demonstrated that the antibody‐dependent cellular cytotoxicity (ADCC) of these cells against O. Rh erythrocytes sensitized with anti‐D IgG is significantly enhanced. The C3 specificity of the process and the role of C3bR's of the target cells: are proved. It is postulated that effector cell‐bound C3b amplifies ADCC by improving effector cell‐target cell contact.
Role of Ia‐Positive Cells in the Lymphocyte Responses to Yersinia
Authors: VUENTO R. , ESKOLA J. , LEINO R. , VIANDER M. , TOIVANEN A.
Published: June 2006

Activation of T lymphocytes by an antigen requires joint recognition of the‐ antigen and the class‐H HLA determinants on the membrane of the antigen‐presenting cells (APC). Patients with reactive arthritis exhibit a depressed lymphocyte transformation response 10 Yersinia, suggesting a possible immunoregulatory disturbance in these patients. In this study the role of Ia (dass‐II HLA antigen)‐positive APC in the lymphocyte response to a complex antigen, whole Yersinia bacterium, was evaluated. The results demonstrate that Ia‐positive cells are necessary for the T‐lymphocyte response to Yersinia. The role of APC in the pathogenesis of reactive arthritis is discussed.