bluuebunny/crossref_metadata_2025 huggingface dataset:
Dextran Sulphate Selectively Enhances Interleukin‐2‐Dependent Cytotoxic T Lymphocyte Growth but Not Differentiation
Authors: PRIMI D. , BERETTA A.
Published: June 2006

We have recently observed that dextran sulphate (D×S) interacts with molecules responsible for terminal B‐cell maturation. Since this property of D×S is most likely due to its anionic characteristics, we have investigated whether this molecule could also modulate the response of cytolytic T cells (CTL) to interleukin‐2‐conditioned medium (IL‐2 CM). Our data demonstrate that D×S synergizes with IL‐2 in supporting the clonal expansion of CTL. Using limiting dilution analysis, we were able to establish that D×S acts directly on IL‐2 CM and not on the responding lymphocytes and that the synergism observed is the result of increases in both clone size and the frequency of CTL precursors. Finally, since we could also demonstrate that D×S selectively affects the growth‐ but not the differentiation‐promoting activity present in IL‐2 CM, our results lend further support to the notion that CTL growth and differentiation are mediated by distinct soluble products. The possible mechanisms by which D×S alters the property of CTL growth‐supporting activity are discussed, together with the pratical implication of our findings.
Establishment of a Long‐Term Cultured Suppressor T‐Cell Line Specific for Guanosine
Authors: IMAI Y. , NAIKI M. , OSAWA T.
Published: June 2006

Induction of suppressor cells specific for gmmosine in C57BL/6 mice with syngeneic spleen cells coupled with guanosine was demonstrated. Spleen cells from mice that had been tolerized by the injection of guanosine‐coupled syngeneic spleen cells (G–SC) were repeatedly stimulated with mitomycin C‐treated G‐SC (MMC‐G‐SC) in vitro. These cells effectively suppressed the secondary in vitro response to guanosine–keyhote limpet haemocyanin (G–KLH) but did not suppress the response to sheep erythrocytes (SRBC). From these cell populations a long‐term‐cultured suppressor T‐cell line specific for guanosine was established by using interleukin‐2 and MMC‐G‐SC. This cell line suppressed the response to G‐KLH but did not suppress the response to trinitrophenyl–KLH and SRBC. The suppressive effect was completely eliminated by treatment with anti‐Thy 1.2 and complement
Modulation of Natural Killer Cell Activity in the Rheumatoid Joint and Peripheral Blood
Authors: COMBE B. , POPE R. , DARNELL B. , TALAL N.
Published: June 2006

Natural killer (NK) cell activity and its regulation in synovial fluid (SF). synovial tissue (ST). and peripheral blood (PB) was studied in 23 patients with active rheumatoid arthritis (RA). NK activity was reduced in PB (P< 0.005), SF (P <0.002), and ST of patients with RA compared to the PB of 28 healthy controls. NK activity in SF was inversely correlated wilh disease activity as measured by erythrocyte sedimentation rate (r=‐0.561; P<0.02). Poly I:C. an Interferon inducer, stimulated NK activity in RA patients' PB and SF and control subjects' PB to similar extents. However, augmentation of NK activity by interleukin‐2 was significantly greater in SF than in PB of RA (P<0.02). Preincubation of mononucleur cells with indomethacin significantly increased the NK activity of normal and RA PB but had no effect on that of SF. These observations suggest that the NK activity may be reduced in both PB and SF of RA and (hat functional differences between populations of cells with NK‐like activity and/or differences in the control or modulation of NK activity exist between PB and SF.
α1‐Microglobulin Glycopeptides Inhibit Antigen‐Specific Stimulation of Human Peripheral Blood Leucocytes
Authors: ÅKERSTRÖM B. , LÖGDBERG L.
Published: June 2006

Glycopeptides were prepared from proteolytically digested human and guinea pig α1 microglobulin (α1‐m) by gel chromatography on Sephadex G‐100 and affinity chromatography on concanavalin A‐Sepharose. Amino acid analysis showed that the average glycopeptide was a tripeptide containing the amino acids aspartic acid/asparagine, isoleucine, and serine and/or threonine. It has earlier been shown that human α1‐m carries two or three N‐glycosidically linked oligosaccharides of the high‐mannose type. These preparations of glycopeptides inhibited the proliferative response of peripheral human blood leucocytes in the antigen purified protein derivative. The dose‐response relationship of the inhibitions showed a greater specific activity of the glycopeptides than of whole α1‐m. Mild alkali treatment of human α1‐m did not affect its specific inhibitory activity, suggesting that the peptide backbone is of little importance for the immunosuppressive effect of α1‐m. No difference in inhibitory activity was seen between human and guinea pig native α1‐m or α1‐m glycopeptides. Human asialo α1‐m exerted a suppressive effect on the antigen‐specific leucocyte proliferation similar to that of native α1‐m.
Isolation of Model Soluble Immune Complexes in the Fluid Phase by Monoclonal Anti‐IgG‐ Ferritin Antibodies
Authors: KNUTSON D. W. , RUDICK R. A. , HERNDON R. M.
Published: June 2006

Ferritin conjugates of monoclonal IgG anti‐human gamma chain (anti‐IgG‐F) were reacted with soluble heat aggregates of IgG (A‐IgG) and with soluble DNA‐anti‐DNA complexes to increase the S rate of the model soluble immunecomplexes (ICx) and thus facilitate isolation of ICx in the fluid phase and provide an immunochemical marker for subsequent ultrastructural analysis. A‐IgG appeared as globular or curvilinear structures withindividual IgG molecules arranged in a random fashion. The technique appears promising for characterization of other soluble ICx.
Interleukin‐1 Production by a Cloned Line of Human Monocyte‐Like Cells (CM‐SM)
Authors: REVOLTELLA R. P. , BUTLER R. H. , MUSIANI P. , PIANTELLI M. , RANELLETTI F. O.
Published: June 2006

Interleukin‐1 (IL‐l) production by the human monocyte‐like cloned cell line CM‐SM has been investigated as a function of the state of cell differentiation. CM‐SM cells were induced to differentiate alone the monocyte‐macrophage lineage by bacterial lipopolysaccharides (LPS) or by 12‐O‐tetradecanoyl‐phorbol‐13‐acetate (TPA). Cell differentiation was studied by various morphological, functional, cytochemical, and immunological variables, whereas IL‐1 activity in the supernatants was measured by the lectin‐primed thymocyte proliferation assay. Unstimulated CM‐SM cells constitutively produced small amounts of IL‐1, and most of the cells appeared relatively undifferentiated. LPS induced cell differentiation, but the effect was reversible, and the cells, in general, did not acquire a capacity for phagocytosis. IL‐1 levels were increased about 10‐fold over the controls. TPA induced further cell differentiation to macrophage‐like cells capable of phagocytosis. IL‐1 activity could not be measured directly in the supernatants owing in thesynergistic effect of TPA in the assay system. Unequivocal removal of the phorbol was not achieved, but the data indicated that the ‘real’ levels of IL‐l in the TPA‐induced cultures were not significantly higher than those from LPS‐induced cultures
Concanavalin‐A‐Activated Lymphocytes Suppress Immune Responses in Vitro but Are Helper Cells in Vivo
Authors: MÖLLER G.
Published: June 2006

In vitro concanavalin A (Con A)‐activaied spleen cells suppressed the primary in vitro immune response of syngeneic spleen cells to sheep erythrocytes (SRBC) but enhanced the in vivo anti‐SRBC responses when transferred to syngeneic untreated mice. Con‐A‐activated spleen cells injected into nude mice enabled these mice 10 respond to SRBC
The Role of Negative Charge in the Complement‐Dependent Dissoeiation of IgG‐Mediated Aggregation
Authors: HED J. , JOHANSSON M. , SKOGH T.
Published: June 2006

The IgG‐medialcd aggregation of yeast particles was used as a model to study the dissociating effect of human serum complement on immune aggregates A 92% decrease in non‐aggregated particles was obtained hy coating particles with UG. After incubation of the aggregates in normal human serum (NHS) at VTC the numher of free particles increased almost 10 times. The ettect could he obtained with ethyleneglycol‐bis‐β‐aminoethyl ether)‐N, N‐tetraaectic acid‐containing serum but not cthylenediaminelciraacetic acid‐containing serum, indicating the importance of The alternate pathway of complement activation. Treatment wilh NHS did nm release anti‐yeast IgG from the particles, indicating that disruption of anitgen‐anlibody bonds did not explain the phenomenonm. The negative charge of the different particles was studied hy measuring the interaction to diethylammuelhyl‐Sephacel heads Compared with non‐coated and IgG‐coated particles, the NHS‐ircated particles were not released until the ionic strength increased to 200 mM NaCl or the pH decreased to 4.4. indicating a strong negative charge of NHS‐ireated panicles. We propose that complement increases the negative charge of immune complexes, thereby inducing repulsive forces that counteract Fc‐Fc interactions and increase the solubility of the complexes
Binding of Human IgA Fragments to Protein A‐Sepharose Studied with an ELISA Method
Authors: BRUIN G. , FABER A. , BIEWENGA J.
Published: June 2006

An enzyme‐linked immunosorbent assay method was developed to investigate the binding of IgA fragments in protein A. The method proved to be specific and highly sensitive. Contamination with IgA did not interfere with the detection of IgA binding to protein A. and less than 10 mg of IgA could be detected. Four of nine IgA proteins tested bound to protein A to different extents. The binding was not disturbed by reduction and alkylation of the IgA proteins. Four‐chain F(abe)2 and F(ab′)2 fragments of the protein A‐reactive IgA proteins also bound to protein A. On reduction and alkylation these fragments formed two‐chain Fabc and Fab′fragments. Of these, Fabc did not bind, whereas doth Fab′and IgAl‐protease‐produced Fab fragments did bind to protein A. These results demonstrate that the Fabh fragment has a binding site tor protein A. It is, suggested that the protein A binding site is located on the CHI domain of the IgAI molecule. On Fabc fragments this binding site may be blocked because of structural alterations.
Glucocorticoids Enhance the in Vitro Ig Synthesis of Pokeweed Mitogen‐Stimulated Human B Cells by Inhibiting the Suppressive Effect of T8+ T Cells
Authors: PAAVONEN T.
Published: June 2006

The in vitro effects of three potent glucocorticoids (GC) (dexamethasone, prednisolone, cortisone) on human lymphocyte functions were investigated. In pharmacological concentrations GC strongly suppressed lymphocyte transformation induced hy T‐eell mitogen (concanavalin A and phytohaemagglutinin). After pokeweed mitogen (PWM) stimulation GC enhanced the number of immunoglobulin (Ig)‐producing cells without affecting the proliferative response. Mineralocorlieoid aldosterone showed no effect. Addition of 3 ± 10‐8‐3 ± 10‐6 mol/1 of different GC to PWM cultures significantly increased the number of Ig‐secreting cells, measured by the plaque‐forming cell assay. Experiments conducted with fractionated defined lymphocyte subpopulations showed that the T8+, a radiosensitive T suppressor cell, is more sensitive than the T4+ T helper cell to GC effects. It is concluded that GC in pharmacological concentrations display a dual effect on human lymphocyte functions in vitro: an inhibition of lectin‐induced T lymphocyte proliferation and a rather selective inhibition of T suppressor cell function which leads to an enhanced B‐cell maturation and Ig synthesis in PWM‐stimulated cultures. No measurable direct effect on the B lymphocytes was noticed.
Effect of Verapamil on T‐Lymphocyte Activation in Vitro
Authors: BRUSERUD Ø.
Published: June 2006

Verapamil, a calcium‐inhibitory drug, was found to inhibit T‐lympocyte proliferation in mixed lymphocyte culture and the proliferate response to phytohaemagglutinin and mumps antigen. It also inhibited production of interleukin 2 (IL‐2). To exert inhibition, verapamil had to he added early in the culture period. Verapamil also had a relatively small inhibitory effect on IL‐2‐dependent growth. The effects were clearly seen only at concentrations exceeding the therapeutic serum level of verapamil.
Isopycnic Ultracentrifugation of Immune Complexes
Authors: RøAHL E.
Published: June 2006

Isopycnic ultracentrifugation is frequently applied for preparative isolation of macromolecules. Using bovine serum albumin (BSA)‐anti‐BSA antibody complexes as a model system. isopycnic bunding of complexes was observed in CsCl. Nycodenz. and sucrose gradients. In CsCl gradients, free antigen or antibody could not be separated from the immune complexes. Variations in antigen to antibody ratio from equivalence and in the amount of complement present during complex formation resulted in zone broadening and banding at slightly lower densities in Nycodenz. This was not observed in sucrose. Serum immune complexes were isolated from patients with rheumatoid arthritis or ankylosing spondylitis. Banding of in vivo‐formed immune complexes was observed more frequently in sucrose than in Nycodenz.
Two Human IgM Myeloma Proteins with Unusual Specificities for Streptococcal Carbohydrate‐Associated Epitopes
Authors: EMMRICH F. , BUNDLE D. , van der ZEE J. , OUT T. , ZENKE G. , EICHMANN K.
Published: June 2006

Five hundred and fifty human sera from patients with IgM myeloma or Waldenström's macroglobulinaemia were screened by a solid‐phase enzyme‐linked immunoassay for binding to the carbohydrate of group A streptococci (A‐CHO). Two of them (AC8 and AC 179) contained immunoglobulin. which bound specifically to A‐CHO even at serum dilutions of 1:107. Using synthetic oligosaccharides coupled to protein for inhibition studies, the fine specificities of AC8 and AC179 were determined. AC179 is directed to α‐linked rhamnose oligosaccharides, AC8 appears to be specific for N‐acetyl‐D‐glucosamine (GlcNAc) side chains β(1→2)‐linked to rhamnose, whereas GlcNAc side chains in A‐CHO are reported to be β(1→3)‐linked to the rhamnose backbone. Naturally occurring anti‐A‐CHO antibodies consist mainly of low‐affinity antibodies to such β(1→3)‐linked GlcNAc. In contrast, both myeloma antibodies show more than 10 times higher relative affinities to A‐CHO than antibodies prepared from normal human serum (anti‐GlcNAc and anti‐A‐CHO, respectively) by selection for high affinity in the elution procedure. AC179 induced complement activation in the presence of A‐CHO.
Non‐Immune IgG F(ab′)2 Binding to Group C and G Streptococci Is Mediated by Structures on γ Chains
Authors: ERNTELL M. , MYHRE E. B. , KRONVALL G.
Published: June 2006

The present investigation was designed to determine whether the heavy or the light immunoglobulin chain is involved in the non‐immune binding of IgG F(ab′)2 fragments to specific surface receptors on human group C and G streptococci. Purified human polyclonal IgG was mildly reduced with dithiothreitol and alkylated with iodoacetamide. Light (L) and heavy (H) chains were separated. Intact IgG and purified L and H chains of polyclonal immunoglobulin G were tested in an inhibition assay for non‐immune IgG F(ab′)2‐mediated binding to group C and G streptococci. H chains inhibited the uptake of isotope‐labelled IgG F(ab′)2 fragments. Isolated L chains were non‐reactive. Intact IgG molecules were more potent inhibitors than isolated H chains tested in equimolar concentrations. These results indicate that the non‐immune interaction between human group C and G streptococci and F(ab′)2 fragments of human IgG is mediated by reactive sites exposed on the immunoglobulin G H chains. The observation that intact IgG on a molar basis was more inhibitory than purified γ chains suggests that the L chains may contribute to the reactivity, presumably by passive stabilization of the immunoglobulin molecule.
In Vivo Isotype Regulation of Humoral Responses to Dextran B1355 in BALB/c Mice Double‐Class IgG3/IgM Producers as a Function of Age
Authors: RIVIER D. A. , TREFTS P. E. , COOK K. A.
Published: June 2006

This report shows that, in 8‐ to 10‐month‐old BALB/c mice immunized intraperitoneally with dextran B1355, approximately 75% of IgG3 anti‐α(l→3) polyglucan (anti‐dex) plaque‐forming cells (PFC) detected in the spleen were identified as double‐Ig class producers secreting simultaneously IgG3 and IgM antibodies with the same specificity for the dex epitope. Under the same conditions of immunization, however, IgA anti‐dex PFC were mostly single‐class secretors. IgA PFC developed in the spleen in highest numbers (equal to IgM), but in Peyer's patches IgA FFC were sevenfold more numerous than IgM. Furthermore, spleen IgG3 anti‐dex PFC responses were low compared with spleen IgA and IgM anti‐dex PFC responses and appeared only late in ontogeny. The possibility is discussed whether a TH dependence of the IgA anti‐dex response and a TH‐independent generation of the IgG3 response are responsible for the different pattern of isotype expression.
H‐2‐Linked Ir Genes Have a Striking Influence on the Immunogenicity of Idiotopes of Myeloma Protein 315 for T Helper Cells
Authors: JøRGENSEN T. , BOGEN B. , HANNESTAD K.
Published: June 2006

H‐2‐linked immune response (Ir) genes control T helper cells (Th) that recognize idiotopes of the V domains of myeloma protein 315 as carriers; Th recognition was detected by augmentation of antibody responses of hapten (4‐hydroxy‐3‐iodo‐5‐nitrophenylacetyl (NIP))‐primed B cells boosted with NIP conjugated to Fab315. The present study indicates that the responder k allele of the Ir VH315 gene maps to the I‐A subregion of H‐2. A responder s allele of the Ir Vλ2315 gene on an A‐strain background was identified, which also most likely maps to I‐A. Although the d allele of the Ir Vλ2315 gene is a responder allele on DBA/2 background, the D2.GD strain (with I‐region haplotype AdBbJbEbCb) was non‐responder to Vλ2315, suggesting either that the responder d allele maps to I‐E or that the b allele of a second Ir Vλ2315 gene located to the right of I‐A exerts a strong suppressive influence. The H‐2b haplotype conferred non‐responsiveness to VH315, Vλ2315, and Fv315.
Adherence of Lysostaphin to and Penetration into Human Monocytes
Authors: van den BROEK P. J. , BUYS L. F. M. , van FURTH R.
Published: June 2006

The effect of lysostaphin on Staphylococcus aureus phagocytosed by monocytes was investigated. The results showed that lysostaphin adheres to monocytes by a temperature‐independent mechanism, is not adequately removed from monocytes by washing, and penetrates by means of a temperature‐dependent mechanism. In in vitro assays of monocyte function, phagocytosed S. aureus can be killed by lysostaphin after penetration of the cells during incubation or by adhering lysostaphin when the monocytes are disrupted.
Appearance of Different Lymphoid Cells in Synovial Tissue and in Peripheral Blood during the Course of Collagen II‐Induced Arthritis in Rats
Authors: HOLMDAHL R. , RUBIN K. , KLARESKOG L. , DENCKER L. , GUSTAFSON G. , LARSSON E.
Published: June 2006

The involvement of different sets of lymphoid cells in the development of collagen II‐induced arthritis in rats was studied by means of immunohistochemical analyses on frozen sections of tissue from joint biopsy specimens taken at different phases of arthritis development. Particular attention was paid to cells involved in early pannus formation. Accumulation of anti‐Ia‐reactive cells close to the cartilage surface was seen early in the development of pannus, and the anti‐Ia reactive cells could in later phases be seen infiltrating cartilage and crowding bone surfaces at sites of marginal erosion. With the help of monoclonal anti‐T‐cell subset antibodies and rabbit anti‐rat immunoglobulin antiserum, it was demonstrated that synovial infiltration of T lymphocytes, particularly W3/25‐reactive T “helper” cells, occurs very early in the development of arthritis, whereas a moderate increase of Ox 8‐positive ‘suppressor/cytotoxic’ T cells and a small number of B cells and plasma cells are seen later in the course of the disease. Levels of Ia‐expressing cells and of T cells belonging lo different subsets were recorded in peripheral blood by means of immunocytochemical analyses on cell smears; no significant deviations from normal levels were seen during the development of arthritis.
Characterization of Chlamydia trachomatis Serotypes by Human T‐Lymphocyte Clones
Authors: QVIGSTAD E. , SKAUG K. , HIRSCHBERG H.
Published: June 2006

T cells primed to Chlamydia trachomatis serolypes A, F. and K were cloned by limiting dilution. All T‐lymphocyte clones obtained reacted only with C. trachomatis antigens. The proliferate capacity of 89 clones was studied with autologous non‐T cells as antigenpresenting cells and the chlamydia serotypes A, B, D, F, K, and LGV‐2 as antigens. Most of the clones reacted to several of the chlamydia strains, indicating common antigenic determinants. Other T‐cell clones reacted with only a few serotypes. On the basis of the proliferation of the T‐cell clones to the chlamydia strains and to interleukin‐2, different reactivity patterns were obtained, which possibly can be used to differentiate among the chlamydia strains.
Terminal Differentiation of Cord Blood Lymphocytes Induced by Thymosin Fraction 5 and Thymosin Alpha1
Authors: HO A. D. , STEHLE B. , DIETZ G. , HUNSTEIN W. , HOFFBRAND A. V.
Published: June 2006

Cord blood lymphocytes (CBL) have been shown to be functionally immature compared with normal circulating adult lymphocytes (NAL). Differentiation of T cells is associated with changes in surface antigenic markers and in the pattern of purine degradative enzymes. Previous studies have demonstrated that thymosin fraction 5 (TMS‐F5) and thymosin alphal (TMS‐α1 can induce in vitro differentiation of murine T‐cell precursors and human thymocytes. We have investigated the effects of TMS‐F5 and TMS‐a, on the pattern of the purine degradative enzymes adenosine deaminase, purine nucleoside phosphorylase, and ecto‐5′‐nucleotidase (5′NT) of CBL and on the phenotypic markers from the OKT series 3,4,8 and 11. Other than a significantly reduced level of 5′NT activity (P<0.001) and an elevated percentage of OKT4+cells (P<0.01), CBL demonstrated the same immunological and biochemical patterns as NAL. Incubation of CBL with TMS‐F5 (150 jug/ml) and TMS‐α1 (1 μ/ml) for 40 h caused a significant rise in 5′NT level and decrease of cells positive for OKT4, resulting in a pattern characteristic of NAL. Thus TMS‐F5 might induce the terminal differentiation of CBL, and TMS‐α1 seemed to be the active component.
Natural Cytotoxicity of Human Lymphocytes against Equine Target Cells in Vitro
Authors: BROSTRÖM H. , OBEL N. , PERLMANN P.
Published: June 2006

Human lymphocytes displayed a frequent natural cytotoxicity (NK) in vitro against normal equine dermal fibroblasts (ED) and against equine tumour cells of a virus‐containing cell line (Mc‐1). Similarly, human normal sera contained antibodies that induced antibody‐dependent cellular cytotoxicity (ADCC) by normal human lymphocytes against the same target cells. Both NK and ADCC varied for different donors. For individual donors, however, cytotoxicity against the two target cells was significantly correlated both in NK and ADCC. For ED there was also a significant correlation between ADCC and NK activity. Both NK and ADCC showed some selectivity as assessed by cold target cell inhibition. Inhibition studies with Fab fragments of anti‐human IgG established the involvement of immunoglobulins in the NK reaction. In this context, a marked and mainly immunoglobulin‐dependent increase in both NK and ADCC activity against Mc‐1 was observed in a laboratory worker frequently exposed to the target cells. The results indicate that variations of natural cytotoxicity in individual donors may sometimes be an indication of an ongoing spontaneous sensitization.
Specific IgM Enhances and IgG Inhibits the Induction of Immunological Memory in Mice
Authors: HEYMAN B. , WIGZELL H.
Published: June 2006

The effect of priming mice with IgM anti‐SRBC (sheep erythrocytes) together with SRBC or IgG anti‐SRBC together with SRBC on the development and expression of memory cells was studied. Mice primed with specific IgM and SRBC showed a much more efficient secondary plaque‐forming cell and serum antibody response after challenge with SRBC in an adoptive transfer system than did controls primed with SRBC only. The expression of this enhanced memory of IgM‐primed spleen cells was counteracted by the high levels of internal IgG anti‐SRBC (also the result of priming with IgM) when the mice, instead of being tested in adoptive transfers, were challenged directly. The antigen‐specific feedback suppression of the primary antibody response by specific IgG antibodies was also seen to inhibit partially the development of memory cells. The suppressive effect on priming could be demonstrated both in adoptive transfer systems and after direct boost of the same mice thai received the primary immunization. Both the IgM enhancement and the IgG suppression of memory cell development were antigen‐specific, since no effect on the antibody response to a non‐cross‐reacting antigen, horse erythrocytes, was seen. The effect of these up‐ or down‐regulations of immunological memory could be demonstrated after secondary injections as long as 90–280 days alter priming.
The Influence of Haematoporphyrin Derivative and Visible Light on Murine Skin Graft Survival, Epidermal Langerhans Cells and Stimulation of the Allogeneic Mixed Leucocyte Reaction
Authors: GRUNER S. , MEFFERT H. , VOLK H.‐D. , GRUNOW R. , JAHN S.
Published: June 2006

The influence of combined photochemical treatment with a haematoporphyrin derivative and visible light on antigen‐presenting cells was evaluated. Treatment of murine skin grafts with this procedure prolonged their subsequent survival on allogeneic recipients. The haematoporphyrin derivative and light decreased the ATPase activity of epidermal Langerhans cells in murine skin. When stimulator cells in a human allogeneic mixed leucocyte reaction were treated with the haemaioporphyrin derivative and light, they lost their stimulatory capacity. It is proposed that the haemaioporphyrin derivative and visible lighl interfere, on analogy with ultraviolet radiation, with the function of antigen‐presenting cells.
Proportions of Ig Classes and Subclasses in Rubella Antibodies
Authors: SARNESTO A. , RANTA S. , VAANANEN P. , MAKELA O.
Published: June 2006

The proportions of six immunoglobulin isotypcs (IgA. IgM. IgGl. lgG2, IgG3. and IgCi4) in rubella antibody responses were quantified in 40 scrum samples (20 patients). The first sample from each patient was taken during the first days of the illness, and the second sample 10±1 days later. A tenfold average increase in antibody concentration was observed between the first and the second sample. IgM was the predominant isotype in the first sample (average, 73% of all antibodies), followed by IgGl (19%). IgA and IgG3 antibodies were detected in only a few of the first samples, and IgG2 or IgG4 in none. In the second samples IgGl was the predominant antibody isotype (average, 59%). Next came IgM (23%), followed by IgA (8%) and IgG3 (3%). No IgG2 or IgG4 antibodies were detected. Although the proportion of IgM antibodies was lower in the second than in the first samples, their concentration increased in all patients (the average factor was 7). The kinetics of the IgA response was irregular. In some patients there was a strong (up to 90‐fold) increase in IgA antibodies, hut in two patients a small drop was delected. The kappa‐ to lamhda‐ehain ratio of rubella antibodies appears to be close to the expected 2:1. It decreased in some patients during the Ml days and increased in others.
Antibodies to Human T Lymphotropic Virus Type III Demonstrated by a Dot Immunobinding Assay
Authors: BIBERFELD G. , BREDBERG‐RÅDEN U. , BÖTTIGER B. , BIBERFELD P. , MORFELDT‐MÅNSSON L. , SUNI J. , VAHERI A. , SAXINGER C. , GALLO R.
Published: June 2006

A dot immunobinding (DIB) technique was applied to the demonstration of antibodies to human T‐lymphotropic virus type III (HTLV‐III). By this technique IgG antibodies to HTLV‐III were demonstrated in six of six Swedish patients with acquired immune deficiency syndrome and in 37 of 39 (95%) Swedish homosexual men with persistent generalized lymphadenopathy but in none of 50 Swedish healthy blood donors. Findings obtained by this method showed complete concordance with those obtained by an enzyme‐linked immunosorbent assay. All sera positive by DIB were also positive by Western blotting. The DIB assay is simple and well suited for screening of sera for HTLV‐III antibodies.
Urinary Immunoglobulins in Healthy Individuals and Children with Acute Pyelonephritis
Authors: EDÉN C. SVANBORG , KULHAVY R. , MÅRILD S. , PRINCE S. J. , MESTECKY J.
Published: June 2006

Urine samples obtained from children with acute pyelonephritis and from healthy children and adults were analysed with regard to the molecular form and specific antibody activity of urinary immunoglobulins. The urinary IgA and IgG levels were quantified in unconcentrated urine by radioimmunoassay. The children with urinary tract infection had significantly higher levels of IgG and IgA than age‐matched controls but not higher than healthy adults. After tenfold concentration, the urine was fractionated on an Ultrogel AcA 22 column, and the IgA, secretory IgA, and IgG in the fractions were determined by radioimmunoassay. IgA in urine from healthy adults was predominantly represented by polymeric IgA linked to secretory component: small quantities of monomeric IgA were also present. IgG eluted in the position of the serum standard. Increased proportions of IgG and monomeric IgA were found in the infected patients. Specific antibody activity of the IgG and IgA classes to antigens of the infecting Escherichia coli strain was detected in whole and in fractionated urine from children with acute pyelonephritis. The specific antibody activity in healthy adults and children was low.
Mumps Virus‐Induced Enhancement of the in Vitro Cytotoxicity of Cord Blood Lymphocytes
Authors: ALSHEIKHLY A.‐R. , ANDERSSON T. , ANDERSSON U. , PERLMANN P.
Published: June 2006

Purified lymphocytes from the umbilical cord of healthy donors (CBL) displayed lower natural cytotoxicity (NK) and antibody‐dependent cellular cytotoxicity (ADCC) than peripheral blood (PBL) from adult donors. In contrast, CBL treated with small amounts of UV‐inactivated or live mumps virions expressed the same level of enhanced cytotoxicity (virus‐dependent cytotoxicity (VDCC)) against non‐infected target cells as PBL. For individual CBL donors there was no correlation between the level of NK and VDCC, indicating involvement of partly distinct effector cell populations. The heterogeneity of the effector cells active in VDCC was confirmed by cell fractionation experiments. The major CBL effector cells in NK and ADCC were found in‘non‐T’lymphocyte fractions and/or in fractions containing cells with high‐avidity receptors for IgG. In contrast, CBL fractions consisting of about 100% lymphocytes bearing T‐cell markers and depleted of FcγR+ cells were strongly cytotoxic in VDCC when T24 cells (human bladder carcinoma) were the targets. With two other target cell types of similar susceptibility to VDCC, the cytotoxic activity of T‐cell‐containing fractions was less pronounced, indicating that the target cells play an active role in effector cell selection. The surface marker profiles of the VDCC effector cells were the same for CBL and adult PBL. Incubation of CBL with UV‐inactivated virions usually gave no significant stimulation of DNA synthesis above that seen in virus‐free controls. Taken together, our results suggest that neither specific recognition of viral antigen by T cells nor mitogenic effects of viral material are involved in VDCC generation.
Virus‐Dependent Cellular Cytotoxicity in Vitro
Authors: ALSHEIKHLY A.‐R. , ANDERSSON T. , PERLMANN P.
Published: June 2006

When human peripheral blood lymphocytes were incubated with 51Cr‐labelled tissue culture cells (T24 bladder carcinoma cells or Chang liver cells), their natural cytotoxicity (NK) usually stopped after 8h of incubation. The 51Cr release induced by lymphocytes treated with small amounts of live or ultraviolet‐inactivated mumps virus was strongly enhanced and lasted longer. When the lymphocytes were fractionated by Percoll gradient centrifugation, the highest NK activity was found in the low‐density fraction enriched in large granular lymphocytes, whereas that of the T‐cell‐enriched high‐density fractions was low. In contrast. the virus‐dependent cellular cytotoxic (VDCC) activity was more evenly distributed between these fractions. However, there was a difference between the target cells in that the T24 cells were more susceptible to the cytotoxicity of lymphocytes in the high‐density fractions than the Chang cells. Studies of Percoll fractions in the single‐cell agarose assay showed that virus treatment increased the proportion of both target binding cells and killer cells in all fractions. Moreover, in the high‐density fractions the increase in the number of killer cells was greater than that in binding cells, suggesting that the enhanced target cell killing induced by the virions reflected both increased binding and effector cell activation. Surface marker analysis of unfractionated lymphocytes indicated that the number of T3+ effector cells was greater than that of the HNK‐1+ effector cells, regardless of whether the lymphocytes were treated with virus or not. However, for both NK and VDCC, the T3 to HNK‐1 distribution ratio on the effector cells was 5–8:1 for T24 and 2:1 for Chang. Taken together, the results indicate that both NK and VDCC effector cells are phenotypically heterogeneous and that the target cells may play an active role in the recruitment of those effector cells that are most efficient in that system. The enhancement of lymphocyte cytotoxicity primarily reflects effector cell recruitment.
Retention of Immune Complexes by Fc Receptors on Mouse Follicular Dendritic Cells
Authors: RADOUX D. , KINET‐DENOËL C. , HEINEN E. , MOEREMANS M. , DE MEY J. , SIMAR L. J.
Published: June 2006

Follicular dendritic cells (FDC) are located inside lymph follicles and are mainly characterized by their capacity to retain antigens. We investigated this aspect in mice lymph nodes by using bovine serum albumin (BSA) labelled with 5‐nm colloidal gold particles and homologous anti‐BSA antibodies bound to 20‐nm gold particles. Gold‐labelled BSA injected alone in non‐immunized mice was only rarely found in FDC cytoplasmic interdigitations. Injected in the form of immune complexes, it was retained by FDC. Antigen‐free anti‐BSA antibodies injected under similar conditions as immune complexes were always found in draining lymph nodes in the same locations as BSA‐anti‐BSA immune complexes. F(ab′)2 from mouse immunoglobulins linked to colloidal gold particles were very rarely found between the FDC extensions, whereas it was intensely phagocytosed by macrophages. Our study permitted precise ultrastructural localization between FDC cytoplasmic extensions or inside macrophages and other cells of the lymph nodes, but it also pointed out that homologous antibodies linked to colloidal gold particles might be retained by FDC in the absence of antigens. These observations, carried out with colloidal gold, were checked by using 125I‐labelled anti‐BSA antibodies. Complement activation determinations of gold‐labelled antibodies or immune complexes showed that antibodies or immune complexes fixed on colloidal gold particles do not activate the complement. This observation enabled us to conclude that Fc receptors play a significant part in the retention of gold‐labelled antibodies or immune complexes by FDC of lymph nodes.
IgE‐Containing Circulating Immune Complexes in Churg‐Strauss Vasculitis
Authors: MANGER B. J. , KRAPF F. E. , GRAMATZKI M. , NÜSSLEIN H. G. , BURMESTER G. R. , KRAULEDAT P. B. , KALDEN J. R.
Published: June 2006

In five patients with vasculitis, hypereosinophilia, and elevated serum IgE levels a diagnosis of Churg‐Strauss syndrome was established. To identify a possible role of IgE in pathogenic mechanisms leading to the vasculitis, we performed a sequential precipitation of the patients'sera with different concentrations of polyethylene glycol (PEG) 6000. Using a radio immunosorbent test, we tested the precipitates obtained for IgE. Considerable amounts of IgE were traced in the serum precipitates of all patients, especially after the second precipitation step (4.0% PEG). In contrast, no IgE‐containing precipitates were detectable in sera from patients with different allergic diseases and high IgE serum levels. Together with an increase in C3d serum levels and the failure to demonstrate Clq‐binding material in patients' sera, these data suggest the involvement of IgE‐containing immune complexes in the pathogenesis of Churg‐Strauss vasculitis, activating the complement via the alternate pathway.
Lymphocyte Transformation Tests and Subpopulations of Lymphocytes in a Population‐Based Material of Atopic Dermatitis in Twins
Authors: LARSEN F. SCHULTZ , GRUNNET N.
Published: June 2006

Lymphocyte function and lymphocyte subpopulations in the peripheral blood have been studied in a population‐based material of 47 twins with atopic dermatitis (AD) (31 with a history of AD, 10 with mild AD, and 6 with moderate AD) and in 47 age‐ and sex‐matched non‐atopic control twins. Lymphocyte transformations to phytohaemagglutinin, concanava‐lin A (Con A), pokeweed mitogen, and purified protein derivative of tuberculin were investigated. Lymphocyte subpopulations were charaterzied by EAET rosettes and the monoclonal antibodies OKT3, OKT4, and OKT8. None of these in vitro tests showed any statistically significant differences between patients and controls. In the rather few individuals with moderate AD there was a statistically insignificant tendency to a decreased Con A stimulation in suboptimal concentration and a reduction of the OKT 8+ cells. However, there were definitely no alterations in the immunological variables between patients with a history of AD and controls. Our results indicate that the investigated variables could be related to disease activity. We suggest that they represent epiphenomena rather than pathogenetic mechanisms of importance for the development of AD.
Effect of UVB on Alloactivating and Antigen Presenting Capacity of Human Epidermal Langerhans Cells
Authors: AUSTAD J. , BRAATHEN L. R.
Published: June 2006

Human epidermal cell suspensions (EC) were obtained by the suction blister technique and enzyme digestion. EC were irradiated in microtitre plates with doses up to 510 mJ/cm2 (2.6 minimal erythemal dose (MED)) by means of fluorescent light bulbs emitting a 280‐320 nm continuous spectrum with a peak at 310 nm. Purified allogeneic T cells were added to the EC immediately or 24 h after radiation. Irradiated EC were pulsed with purified protein derivative (PPD) for 90 min immediately or 24 h after radiation and then cocultured with purified autologous T cells. PPD‐pulsed EC were also irradiated before being cocultured with autologous T cells. Pretreatment of EC suspensions with anti‐DR antiserum plus complement abolished both the alloactivating and the antigen‐presenting capacity, indicating that the DR‐positive Langerhans cells are mainly responsible for these functions. There were no differences in the number of DR‐positive cells in EC before or immediately after radiation. A statistically significant and UV‐dose‐dependent reduction of the alloactivating ability of EC was found both when allogeneic T cells were added immediately and when they were added 24 h after radiation. Likewise, a significant and dose‐dependent reduction of the PPD‐specific T‐cell response was obtained in cultures when using irradiated EC that were PPD‐pulsed immediately or 24 h after radiation. EC that were first PPD‐pulsed and then irradiated induced a significantly increased T‐cell response after low UV doses (1 or 2 MED), whereas higher doses induced a significant reduction of the T‐cell responses.
Interferon Regulation of DR Antigen Expression and Alloantigen‐Presenting Capabilities of the Promyelocytic Cell Line HL60
Authors: STEEG P. S. , SZTEIN M. B. , MANN D. L. , STRONG D. M. , OPPENHEIM J. J.
Published: June 2006

Our research suggests that interferon may have an immunoregulatory role in the initiation phase of immune responses. Recent evidence has demonstrated that lymphokines regulate monocyte cell surface expression of DR antigens and, consequently, the ability of monocytes to activate T lymphocytes in an antigen‐specific manner. In this report cloned interferons and a homogeneous cell line were used to demonstrate that interferon possesses these immunoregulatory functions. Cells of the promyelocytic cell line HL60, when incubated in vitro with recombinant gamma (IFN‐γ) and with alpha interferons (IFN‐α), expressed enhanced levels of DR antigen as determined by both cytotoxicity and fluorescence‐activated cell sorter analyses. Lower concentrations of IFN‐γ than IFN‐α were needed to induce DR expression, and a higher percentage of monocytes were induced to express DR antigen by IFN‐γ than IFN‐α. HL60 cells preincubated with lymphocyte‐derived lymphokines or IFN‐α also stimulated a significantly better in vitro allogeneic response in the mixed leukocyte reaction than untreated HL60 cells. Thus, interferon enhanced both the phenotypic expression of DR antigens of HL60 cells and their functional ability to inititiate T‐lymphocyte responses to an alloantigen.
Morphological Characterization of the Somatostatin‐Immunoreactive Dendritic Skin Cells in Urticaria Pigmentosa Patients by Computerized Image Analysis
Authors: JOHANSSON O.
Published: June 2006

By means of computerized image analysis, the somatostatin‐immunoreactive epidermal and dermal dendritic cells of certain urticaria pigmentosa patients were characterized. The evidence obtained supported the concept that the epidermal cells correspond to the Langerhans cells.
Human Epidermal Cell‐Induced Generation of Alloreactive Cytotoxic T‐Lymphocyte Responses against Epidermal Cells
Authors: FAURE M. , DEZUTTER‐DAMBUYANT C. , SCHMITT D. , GAUCHERAND M. , THIVOLET J.
Published: June 2006

Human epidermal cells act as stimulators in the mixed‐skin cell lymphocyte culture reaction (MSLR). To analyse the generation in MSLR of alloreactive cytotoxic T lymphocytes (CTL) in cell‐mediated cytolysis of human epidermal cells, a phenomenon suggested by various observations of skin inflammatory processes in vivo, 18‐h 51Cr‐release assays against epidermal cells cultivated on collagen‐coated plates (epidermal cells autologous to the stimulator cells in MSLR) were conducted after allogenic human MSLR. To analyse the role of human Langerhans cells and related epidermal dendritic cells, which are the only cells expressing the DR‐Ia‐like (class II) antigens in normal epidermis and in suspensions of normal epidermal cells, MSLR and CTL assays were conducted with, as stimulator cells, suspensions of normal human epidermal cells as controls, and, in parallel, suspensions of epidermal cells after preincubation with anti‐class II monoclonal antibody and complement. The generation of alloreactive CTL to epidermal cells occurred only after allogenic MSLR and when targets and stimulator cells were from the same donor; it was abolished when epidermal cell suspensions used in MSLR were depleted in HLA‐DR‐expressing cells. These findings demonstrate that an epidermal cell‐induced generation of cell‐mediated cytotoxicity to human epidermal cells may occur in vitro. Langerhans cells and other class II antigen‐expressing epidermal cells (dendritic indeterminate cells) are necessary for an optimal in vitro sensitization in MSLR and the subsequent generation of alloreactive CTL towards epidermal cells in man.
The Ultrastructure of Initial Changes in Hapten‐Exposed Rat Oral Mucosa
Authors: AHLFORS E. E. , LARSSON P. Å.
Published: June 2006

The experimentally induced cell‐mediated immune reaction has been examined ultrastructurally in rat oral mucosa, using DNCB/DNFB as haptens. In skin‐presensitized animals, an increased number of mononuclear cells was found in the epithelium at a very early phase (15‐60 min) after hapten exposure. In nonsensitized animals, an increased number of cells was evident in hapten‐exposed tissue also very early in the reaction. Mononuclear cells appeared in the connective tissue but very few in the epithelium. Interaction between mononuclear cells and Langerhans cells could be demonstrated in both experimental groups.
Characterization of Immunoregulatory Cytokines Produced by Epidermal Cells
Authors: LUGER T. A. , KOCK A. , DANNER M.
Published: June 2006

The epidermis has been identified as an important site for the initiation of immunological events. In addition to the macrophage‐like Langerhans cells, keratinocytes within the epidermal cells have been shown to act as immunoregulatory cells through the secretion of cytokines such as epidermal cell‐derived thymocyte‐activating factor (ETAF) and interleukin 3. Epidermal cell‐derived interleukin 3 (EC IL‐3), like lymphocyte‐derived IL‐3, induced the proliferation of IL‐3‐dependent mast cell‐like cell lines. Biochemically, EC IL‐3 was a heat‐stable protein with a molecular weight of approximately 30 kD. Upon chromatofocusing, EC IL‐3 exhibited three isoelectric points, at pI 7.8, 7.4, and 7.1. Furthermore, an antiserum against IL‐3 neutralized EC IL‐3 activity, suggesting that the molecules are closely related and share similar epitopes. ETAF‐like macrophage‐derived interleukin 1 (IL‐1) is a low molecular weight protein with a multiplicity of amplifying effects on immunological and inflammatory reactions. Thus BALB/c mice were immunized with partially purified IL‐1, and immune spleen cells were hybridized with plasmocytoma cells. Supernatants of the hybridoma cultures were screened for their capacity to inhibit IL‐1‐induced thymocyte proliferation. After expansion and cloning, one clone was selected for ascitic antibody production. The monoclonal anti‐IL‐1 antibody inhibited both the IL‐1‐dependent thymocyte and the fibroblast proliferation. Furthermore, the antibody blocked murine and human ETAF activity, suggesting that ETAF and IL‐1 share antigenically similar domains. Moreover, by using the monoclonal antibody bound to Staphylococcus aureus cells, it was possible to immunoprecipitate IL‐1. In contrast, anti‐IL‐1 antibody did not inhibit IL‐2 or IL‐3 activity. These findings demonstrate that the production of immunoregulatory cytokines is not confined to cells of the immune system and that keratinocytes through the production of ETAF and EC IL‐3 may mediate inflammatory and hypersensitivity reactions. Furthermore, the monoclonal anti‐IL‐1 antibody may provide a useful tool for the development of new immunoassays to detect IL‐1/ETAF and thereby facilitate the investigation of the role of these cytokines during the pathogenesis of inflammatory diseases.
The Effect of Grenz Rays on the Expression of Allergic Contact Dermatitis in Man
Authors: LINDELÖF B. , LIDÉN S. , LAGERHOLM B.
Published: June 2006

To investigate the effect of grenz rays on the expression of allergic contact dermatitis, six patients hypersensitive to nickel were studied. They were given 3 Gy of grenz rays, once a week for 3 weeks, to a defined area of the back. Twenty‐four hours after the last treatment serial dilution nickel patch tests were applied on the grenz‐ray‐treated area and on untreated control skin. There was an almost total suppression of the allergic contact dermatitis at the site of grenz ray treatment. Biopsy specimens were taken from nickel‐challenged and unchallenged skin, both from the grenz‐ray‐treated area and from the control area. Different cell populations in epidermis and dermis were identified by monoclonal antibodies (Leu 2, 3, 4, 7, Leu M1, B1, OKT6). In the grenz‐ray treated epidermis there was a pronounced reduction of OKT6‐positive cells, regarded as Langerhans cells. No other differences were observed between control and grenz‐ray‐treated skin. Our results suggest that Langerhans cells might be required also for the effector phase of the allergic contact dermatitis.