bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction of tolerance in peripheral T cells with monoclonal antibodies
Authors: Qin Shixin , Wise Matt , Cobbold Stephen P. , Leong Louise , M. Kong Yi‐Chi , Parnes Jane R. , Waldmann Herman 
Published: March 2007

AbstractOur goal has been to develop ways to tolerize the mature immune system to any defined antigen. In this report we show that peripheral (post‐thymic) T cells of mice can become tolerant to a range of antigens (human and rat immunoglobulins, and bone marrow and skin grafts that differ at multiple minor transplantation antigens). In the case of human gamma globulin (HGG), this required that the antigen be given under the cover of a short course of non‐depleting anti‐CD4 antibody, while for tolerance to skin and marrow grafts anti‐CD8 antibody was also required. Tolerance to HGG could be reinforced by repeated injections of HGG, but was lost in the absence of any further exposure to antigen. This reversal of tolerance with time was due to new Tcells being exported from the thymus, as it was not observed in tolerized, adult thymectomized mice. In contrast, tolerance to marrow and skin grafts was permanent, presumably because the established grafts acted as a continuous source of antigen to reinforce the tolerant state. Tolerance could not be broken by the infusion of unprimed spleen cells and in one example (tolerance to Mls‐1a) there was clear evidence that specific peripheral T cells were anergic. We propose that anergic cells may themselves participate in reinforcing the tolerant state by competing at sites of antigen presentation.
Differential effects of anti‐CD45 monoclonal antibody on human B cell proliferation: a monoclonal antibody recognizing a neuraminidase‐sensitive epitope of the T200 molecule enhances anti‐immunoglobulin‐induced proliferation
Authors: Alsinet Emili , Inglés‐Esteve Julia , Vilella Ramón , Lozano Francisco , Milá Jordi , Rojo Isabel , Martorell Jaume , Vives Jordi , Gayá Antoni 
Published: March 2007

AbstractWe have generated seven monoclonal antibodies (mAb) that recognize the T200 molecule. These mAb have been classified by competitive binding assay in flow cytometry into three groups each reacting with a different epitope of the T200 molecule: (a) 136‐4B5, that shows a sialic acid nature, (b) 135‐4H9, 135‐4C5, 144‐2, 155‐2 and (c) 72‐5D3, 124‐2H12b. A heterogeneous effect was observed when they were tested on an anti‐immunogiobulin‐induced B cell proliferation. Whereas 72‐5D3 and 135‐4H9 mAb inhibited the proliferative response of B cells, 136‐4B5 mAb greatly enhanced it, both effects being dose dependent. We can conclude that anti‐CD45 mAb have a different and contrary functional behavior on anti‐Ig‐induced B cell proliferation, depending on the epitope recognized. The basis for such a difference could reside in the glucidic nature of the epitope recognized by the 136‐4B5 mAb.
Expression of the human Vβ8 gene product preferentially correlates with class II major histocompatibility complex restriction specificity
Authors: Imberti Luisa , Sottini Alessandra , Spagnoli Giulio , Primi Daniele 
Published: March 2007

AbstractWe report that, in peripheral blood T cells, the Vβ8 gene product is much more represented on CD4+CD8− than on CD4−CD8+ lymphocytes. This skewing was observed in all individuals tested and with two independent strategies, one of which allows the selection of Vβ8+ T cells independently from their major histocompatibility complex‐antigen specificity. Our data imply that the human Vβ8 gene product confers class II restriction specificity and that both the T cell receptor chains and CD4 molecule are involved in the selection of the T cell repertoire.
Human IgG subclass pattern of inducing complement‐mediated cytolysis depends on antigen concentration and to a lesser extent on epitope patchiness, antibody affinity and complement concentration
Authors: Michaelsen Terje E. , Garred Peter , Aase Audun 
Published: March 2007

AbstractThe relative complement‐mediated lytic capability of the IgG subclass isotypes was studied using a matched set of mouse‐human chimeric anti‐(4‐hydroxy‐3‐nitrophenyl)acetyl (NP) antibodies. The subclass pattern was shown to be highly dependent on variations in antigen concentration and to lesser extent on variation in epitope patchiness, antibody binding affinity and complement concentration. In general, the IgG3 subclass was most effective in inducing cytolysis at the different conditions used and only at high antigen concentration did the IgG1 subclass mediated more efficient cytolysis than IgG3. The IgG2 isotype required a relative high antigen concentration to be cytolytic while the IgG4 isotype was not cytolytic at any of the conditions tested. These individual characters of each of the IgG subclasses makes it conceivable that a subtle system of immunoregulation exists among the subclasses.
Thymus colonization in the developing mouse embryo
Authors: Palacios Ronald , Samaridis Jacqueline 
Published: March 2007

AbstractWe have directly followed the formation of and the thymus colonization by pro‐T lymphocytes in the developing C57BL/6 mouse embryo by using the monoclonal antibody JORO 37‐5 specific for pro‐T lymphocytes, immunofluorescence staining and flow fluorocytometry or microscopy analysis. The results show that JORO 37‐5+ cells begin to appear in the liver at day 9 of gestation. These JORO 37‐5+ cells migrate to and colonize the thymus 1 day later, where they expand vigorously during the next 4–5 days and, subsequently, switch off expression of JORO 37‐5 as they further differentiate into mature thymocytes.
Nerve growth factor specifically induces human IgG4 production
Authors: Kimata Hajime , Yoshida Akira , Ishioka Chihiro , Kusunoki Takashi , Hosoi Susumu , Mikawa Haruki 
Published: March 2007

AbstractThe effect of nerve growth factor (NGF) on human IgG4 production was studied. NGF specifically enhanced IgG4 production in cultures of human tonsillar mononuclear cells without affecting production of other isotypes or other IgG subclasses. Optimal enhancement of IgG4 production by NGF required the presence of T cells. However, NGF induced significant IgG4 production by small resting B cells in the absence of T cells, and this production was enhanced by stimulation with Staphylococcus aureus Cowan strain I (SAC). In contrast to small B cells, large activated B cells produced IgG4 spontaneously; this production was enhanced by NGF. NGF also enhanced IgM and IgA production by large B cells, while production of IgG1, IgG2, IgG3 and IgE was not affected. The enhancement of IgG4 production was blocked by anti‐NGF serum but not by control serum. NGF, T cells and SAC, separately or together, failed to induce IgG4 production by surface (sIgG4+)‐depleted B cells. In contrast to NGF, other recombinant human cytokines including interleukin (IL) 1β, IL 2, IL 4, IL 5, IL 6, granulocyte‐macrophage colony‐stimulating factor, interferon α and γ failed to induce IgG4 production. These results suggest that NGF directly and preferentially stimulates activated sIgG4+ B cells to produce IgG4.
Parameters affecting the immunogenicity of a liposome‐associated synthetic hexapeptide antigen
Authors: Frisch Benoit , Muller Sylviane , Briand Jean Paul , Van Regenmortel Marc H. V. , Schuber Francis 
Published: March 2007

AbstractThe effect of liposome association on the immunogenicity of the hexapeptide IRGERA was investigated. When administered in the absence of a carrier and adjuvant this peptide, which corresponds to a linear epitope located at the C‐terminus of histone H3, was not immunogenic. When mice were immunized with the peptide covalently linked to the surface of small unilamellar vesicles containing monophosphoryl lipid A as adjuvant, a relatively long‐lasting response with memory cell induction was observed. The anti‐peptide antibodies raised in this way reacted with the cognate sequence in the native histone. In contrast, coupling of the peptide to the surface of large vesicles yielded both an IgM and IgG response of short duration whereas encapsulation of the free peptide in large vesicles was ineffective. These results indicate that with short synthetic peptides, liposomes provide a substitute for a carrier protein. However, an adjuvant has to be incorporated in the vesicles in order to obtain an efficient immune response. Such an approach may be useful for designing synthetic vaccines.
A single amino acid substitution in the Ak molecule fortuitously provokes an alloresponse
Authors: Dellabona Paolo , Wei Bing‐Yuan , Gervois Nadine , Benoist Christophe , Mathis Diane 
Published: March 2007

AbstractWe discovered by chance that the R28 T cell hybridoma has dual specificity. It responds to a peptide derived from ribonuclease presented by cells displaying Ak molecules and it reacts, in the absence of added antigen, to cells expressing Ak complexes with a single amino acid substitution at position 69 of the α chain. Modelling and functional studies suggest that residue 69 is a peptide contact residue, prompting the hypothesis that R28′s alloreactivity is a cross‐reactive response to an unknown peptide bound in the ‘groove’ of the mutant Ak complex. In this report, we employ a competition assay to confirm that this alloresponse involves a groove‐binding peptide, demonstrate that this peptide derives from or depends on fetal calf serum and exploit a panel of antigen‐presenting cell lines – each displaying an Ak complex with a different position 69 substitution – to establish that the alloresponse is not just a heteroclitic response to ribonuclease, itself. We speculate that much of the alloreactivity against murine class II molecules that is revealed in vitro may prove to be directed at bovine serum‐derived peptides, suggesting that in this context, alloreactivity is a misnomer.
Cyclosporin A renders target cells resistant to immune cytolysis
Authors: Hudnall S. David 
Published: March 2007

AbstractExposure of cytolytically susceptible human target cells with therapeutic concentrations of the immunosuppressive drug cyclosporin A renders these cells highly resistant to T cell‐mediated, natural killer (NK) cell‐mediated, and complement‐mediated cytolysis. The resistance is dose dependent, time dependent and reversible. The resistance is accompanied by target cell growth inhibition as measured by thymidine uptake. Surprisingly, target cell growth inhibition induced by serum depletion is associated with cell‐mediated cytolytic resistance. These data suggest that cyclosporin A (CsA) may block some target cell biochemical pathway(s) important in the suicidal cytolytic process which is (are) linked to some G0/G1 cell cycle events. In addition, these results suggest that the increased risk of Epstein‐Barr virus (EBV)‐associated lymphoproliferative disease in human organ transplant recipients may be contributed to by CsA‐induced resistance of EBV‐transformed B lymphocytes to immune cytolysis.In the post‐transplant setting, CsA probably blocks T cell‐dependent responses to EBV‐transformed B lymphocytes (Bird, A. G., McLachlan, S. M. and Britton, S., Nature 1981. 289: 300) yet leaving the NK cell and antibody‐dependent responses intact (Shao‐Hsien, C. et al., Transplantation 1983. 35: 127). However, given the direct effect of CsA upon EBV‐transformed B lymphocytes, these cells would be rendered resistant to nearly all forms of cytolytic immune control (cytotoxic T lymphocyte, natural killer, antibody‐dependent cell‐mediated cytotoxicity, complement). Unregulated EBV‐transformed B lymphocytes may then proliferate in the CsA‐treated host thus leading to a polyclonal B cell hyperplasia. Our data would suggest that this early pre‐malignant process is likely to be reversible following CsA dose reduction. Indeed, EBV‐dependent polyclonal B cell hyperplasia is seen in early post‐transplant lymphoproliferative disorders (Hanto, D. W., et al., Transplantation 1989. 47: 458). Furthermore, in some cases CsA dose reduction does lead to disease regression (Starzl, T., et al., Lancet 1984. i: 583). However, further progression of the disease probably occurs following chromosomal changes leading to oncogene activation and might be resistant to CsA dose reduction.
Cytokine interactions in experimental cutaneous leishmaniasis. Interleukin 4 synergizes with interferon‐γ to activate murine macrophages for killing of Leishmania major amastigotes
Authors: Bogdan Christian , Stenger Steffen , Röllinghoff Martin , Solbach Werner 
Published: March 2007

AbstractWe investigated the effect of recombinant murine interleukin 4 (IL 4) in the absence or presence of recombinant murine interferon‐γ (IFN‐γ) on adherent bone‐marrow macrophages (MΦ), peritoneal exudate and resident peritoneal MΦ from susceptible BALB/c MΦ, which were pulse‐infected with Leishmania major amastigotes (AM). IL 4 (5–100 U/ml) failed to activate any of these MΦ populations for killing of intracellular AM. However, in the presence of low concentrations of IFN‐γ (10–20 U/ml), which alone caused only a slight or intermediate reduction of the number of intracellular parasites, IL 4 led to a dramatic increase of the parasite elimination by all MΦ populations. In the case of resident peritoneal MΦ, the synergism of IFN‐γ and IL 4 required the incubation of the MΦ with both cytokines or with IFN‐γ alone for at least 10 h prior to infection; adding both cytokines after infection of the MΦ did not cause a significant reduction of the intracellular parasite burden. The synergistic effect of IL 4 and IFN‐γ was completely abrogated in the presence of anti‐IL 4 antibodies. Furthermore, there was no significant difference between MΦ derived from either susceptible BALB/c or from resistant C57BL/6 mice. Evidence is presented that the synergistic action of IL 4 and IFN‐γ occurs via an L‐arginine‐dependent killing pathway. From these data we conclude that IL 4 provides a strong stimulus for the killing of intracellular L. major AM provided low concentrations of IFN‐γ are present. Also, IFN‐γ is apparently an important priming signal for the activation of resident MΦ to eliminate intracellular AM.
Evidence for differential responsiveness of human CD5+ and CD5− B cell subsets to T cell‐independent mitogens
Authors: Zupo Simona , Dono Mariella , Azzoni Livio , Chiorazzi Nicholas , Ferrarini Manlio 
Published: March 2007

AbstractTonsillar resting B cells were separated into CD5+ and CD5− cell subsets and stimulated with the thymus‐independent mitogens, Staphylococcus aureus Cowan strain I (SAC) or insolubilized anti‐μ monoclonal antibodies (aμAb). CD5+ cells incorporated [3H]thymidine more efficiently than unfractionated cells when stimulated with SAC and their response was augmented by the addition of interleukin (IL)2 to the cultures. CD5+ cells also proliferated in response to aμAb provided that IL 2 was present. SAC‐, but not aμAb‐stimulated CD5+ cells produced IgM and IgG molecules when IL 2 was added to the cultures and also secreted autoantibodies with rheumatoid factor activity and sometimes also with anti‐single‐stranded, but not double‐stranded, DNA activity. The efficient response of CD5+ cells was not explained by the fact that they contained cells already activated in vivo. Thus, they did not express the CD23, CD69, CD71 and CD39 activation markers, failed to incorporated [3H]thymidine and to secrete Ig spontaneously or in response to IL 2 and were found to be in a quiescent state by cell cycle flow cytometric analysis.In contrast to CD5+ cells, CD5− cells displayed very little or no [3H]thymidine incorporation in response to SAC or to aμAb and their poor responsiveness was not altered by changing either the doses of the stimulants, the timing of the cultures, by co‐culturing the cells together with CD5+ cells, or by adding IL 2 or IL4. Immunofluorescence studies showed that freshly prepared CD5− cells did not have surface activation markers but that they expressed them following SAC stimulation. Thus, unlike that observed for CD5+ cells, SAC seems to be capable of activating CD5− cells but does not appear to be a sufficient stimulus for driving the cells into the subsequent phases of the cell cycle.The above findings, that demonstrate marked differences in the response to CD5+ and CD5− cells to thymus‐independent stimuli, may bear relevance for the understanding of the normal clonal expansion of CD5+ cells as well as for the pathogenesis of autoimmune diseases.
Suppressor cells of popliteal lymph node origin are involved in the in vivo and in vitro control of experimental allergic encephalomyelitis effector cells in the Lewis rat
Authors: Chabannes Dominique , Borel Jean F. 
Published: March 2007

AbstractLewis rats immunized in the hind footpads with total guinea pig spinal cord tissue in mycobacteria‐enriched complete Freund's adjuvant develop chronic relapsing experimental allergic encephalomyelitis. It was previously shown that popliteal lymph node cells (LNC) isolated at the time of the first recovery (day 16) and transferred into naive syngeneic recipients protect from active induction of the disease. On the other hand, inguinal LNC taken at the onset of the disease (day 11) induce under similar conditions an acceleration of the appearance of the clinical symptoms. In this report, we show that the in vivo suppressive activity of popliteal LNC is associated with the absence of production of interleukin 2 in this compartment. The lack of production of this lymphokine and the suppressive activity can be detected only in the popliteal compartment and appear as early as day 11 after immunization. We show that this suppressive population displays in vitro inhibitory activity on the proliferative response of the disease effectors (inguinal LNC) to guinea pig myelin basic protein. This suppressive activity is not abrogated by addition of interleukin 2, suggesting that these suppressor cells do not inhibit the proliferation by absorption of the released lymphokine or by inhibition of its production.
Mycobacterial proliferation in macrophages is prevented by incubation with lymphocytes activated in vitro with a mycobacterial antigen complex
Authors: Beschin Alain , Cocito Carla , Brijs Lea , de Baetselier Patrick 
Published: March 2007

AbstractAntigen A60 from Mycobacterium bovis bacillus Calmette Guérin was shown to trigger both humoral and cellular immune reactions. We explored the ability of A60 to block intracellular proliferation of phagocytosed mycobacteria with a model system involving peritoneal murine macrophages infected with Mycobacterium avium. Mixed lymphocytes from lymph nodes of mice inoculated with A60 hindered intracellular proliferation of this mycobacterium, owing to A60‐specific cells, proliferation of which was induced in vitro in an antigen concentration‐dependent manner. The lymphokines released by A60‐stimulated T lymphocytes in vitro were identified as interleukin 2 (IL 2) and interferon‐γ (IFN‐γ) : their production showed a clear A60 dose dependence. When supernatants of such induced lymphocyte cultures were incubated with anti‐IFN‐γ antibodies, macrophage activation was prevented, whereas anti‐IL 2 immunoglobulin had little effect. Treatment of infected macrophages with recombinant IFN‐γ reduced intracellular proliferation of mycobacteria, while exogenous IL 2 and tumor necrosis factor were ineffective. Therefore, A60 elicits in vitro proliferation of T lymphocytes responding specifically to this antigen with production of IFN‐γ, which in turn activates macrophages and prevents mutiplication of phagocytosed mycobacteria.
Characterization of immature CD4+CD8−CD3− thymocytes
Authors: Hugo Patrice , Waanders Gary A. , Boyd Richard L. , Scollay Roland , Petrie Howard T. 
Published: March 2007

AbstractPreviously we have described (Hugo, P. et al., Int. Immunol. 1990. 2: 209) an immature CD4+CD8−CD3− thymocyte subset which is thought to be the counterpart of the CD4−CD8+CD3− subset. In this study we show that the ontogeny of these two subsets is parallel in fetal thymic organ culture. Extensive phenotypic characterization of CD4+CD8−CD3− cells reveals that they closely resemble CD4−CD8+CD3− thymocytes being: HSAhigh, Thy‐1high, interleukin 2 receptor α chain negative, CD44−, H2K+/−, CD5low, MEL‐14low/intermediate, CD2+, LFA‐1+ and MTS 35+. Finally, we show that the proportion of CD4+CD8−CD3− thymocytes is highly variable between mouse strains.
Lack of anti‐DNA precursors in λ chain‐bearing B Iymphocytes in (NZB × NZW)F1 mice. Evidence for the contribution of Vχ genes to anti‐DNA specificity
Authors: Lacour Mare , Izui Shozo 
Published: March 2007

AbstractWe have analyzed by the limiting dilution assay on spleen cells from (NZB × NZW)F1 hybrid mice the repertoire of lipopolysaccharide‐responsive murine χ‐ and λ1‐secreting B cells committed to the production of anti‐DNA autoantibodies to determine the contribution of the heavy and light chains to anti‐DNA specificities. Our results demonstrated that anti‐DNA precursors were predominantly found in the χ‐secreting B cell population, but not in λ‐secreting B cells, while anti‐hapten, dinitrophenyl, and anti‐tetanus toxoid activities were distributed fairly well in both populations of B cells. This suggests that the Vχgene segments are critically involved in the generation of anti‐DNA specificities, and that at least at the germ‐line gene level, the heavy chain V region genes by themselves are not able to confer the anti‐DNA autoreactivity.
Islet‐infiltrating T cell clones from non‐obese diabetic mice that promote or prevent accelerated onset diabetes
Authors: Pankewycz Oleh , Strom Terry B. , Rubin‐Kelley Vicki E. 
Published: March 2007

AbstractIn humans and non‐obese diabetic mice (NOD), insulin‐dependent diabetes mellitus (IDDM) results from a spontaneous T cell‐dependent autoimmune destruction of insulin‐producing pancreatic β cells. Previous data suggest that a delicate balance between autoaggressive T cells and suppressor‐type immune phenomena determine whether expression of autoimmunity is limited to insulitis or progresses to IDDM. To resolve the cellular basis of this intricate network of pathogenic CD4+ and CD8+ T cells and the role of T cells in suppressive immune phenomena, T cell clones were propagated directly from islets of NOD mice at the onset of insulitis. Insofar as insulitis, but not IDDM, is universal in NOD mice, we have screened for the in vivo effects of the islet‐infiltrating T cell clones upon expression of IDDM, not insulitis. A CD4+ T cell clone, IS‐3S7D, proliferates in response to islet antigen(s) and its transfer into prediabetic NOD mice promotes the rapid onset of IDDM. An interleukin 2 (IL 2)‐dependent noncytolytic, Vβ11+ CD8+, T cell clone, IS‐2.15, prevents an accelerated onset diabetes in two distinct models. The present study, which documents the presence of CD4+ diabetogenic T cell clones and CD8+ T cell clones that dampen autoimmunity, gives tangible evidence that opposing autoimmune processes may determine whether an autoimmune‐prone host develops frank disease.