bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protective effect of cyclosporin A on immune abnormalities observed in the murine acquired immunodeficiency syndrome
Authors: Cerny Andreas , Merino Ramon , Makino Masahiko , Waldvogel Francis A. , Morse Herbert C. , Izui Shozo 
Published: March 2007

AbstractThe murine leukemia viruses (MuLV) designated LP‐BM5 induce an immuno‐deficiency disease in susceptible strains of mice with many features in common to human acquired immunodeficiency syndrome (AIDS), including lymphadenopathy and profound immunodeficiency associated with enhanced susceptibility to infection and terminal B cell lymphomas. The disease, termed murine AIDS (MAIDS), crucially depends on the presence of B cells and CD4+ T cells, suggesting that mutual activation of these two cell types is central in the pathogenesis of the immunodeficiency syndrome. Cyclosporin A (CsA), whose immunosuppressive effect is attributed mainly to inhibition of interleukin 2 and interferon‐γ expression, interferes in T‐B cell interactions. Here we show that chronic treatment with CsA (40 or 60 mg/kg/day) before and after infection with LP‐BM5 MuLV protects against the development of immunodeficiency disease as assessed by functional, serological and histopathological criteria. The protection was not complete, suggesting both CsA‐sensitive and CsA‐resistant components to the pathogenesis of this syndrome, and was found to be independent of ecotropic MuLV expression. These results underline immunopathological mechanisms in the progression of immune abnormalities in MAIDS that are susceptible to inhibition of CsA and may serve as an experimental basis for developing a treatment of the human disorder with immunomodulators.
Resistance to collagen‐induced arthritis in Biozzi mice is not associated with T cell receptor Vβ gene polymorphism
Authors: Vidard Laurent , Roger Thierry , Bouvet Jean Pierre , Couderc Jacques , Seman Michel 
Published: March 2007

AbstractH‐I and H‐II high antibody‐responder Biozzi mice, which express the H‐2q permissive haplotype, were shown to be sensitive and refractory to collagen‐induced arthritis, respectively. To assess a possible role of T cell receptor (TcR) Vβ gene deletion or polymorphism in the resistance to arthritis in H‐II mice, the germinal structure of TcR Vβ genes and their expression at the membrane level were compared in both lines. In contrast to H‐2q refractory SWR mice, which exhibit a deletion of about 50% of TcR Vβ gene segments, H‐I and H‐II lines have an identical and complete set of Vβ genes and exhibit no difference in the average expression of Vβ6, Vβ8 and Vβ11 gene products on T cell surface. These results indicate that mechanisms other than Vβ gene deletion or polymorphism can be involved in the resistance of H‐2q‐positive mice to experimental arthritis.
Alternative complement pathway‐mediated myeloid cell cytotoxicity: Repertoire of membrane factors participating in regulation of C3 deposition and cytolysis
Authors: Matsumoto Misako , Sugita Yuji , Seya Tsukasa 
Published: March 2007

AbstractMost human nucleated cells and cell lines possess C3 step regulators, decayaccelerating factor (DAF; CD55) and membrane cofactor protein (MCP; CD46) and an inhibitor of membrane attack complex (MAC) formation (p18; CD59). Unless DAF and MCP were simultaneously blocked by their antibodies, Mg2+‐EGTA‐human serum treatment did not induce C3 deposition on most nucleated cells. Furthermore, < 20% lysis occurred even after the block of all the three factors. In contrast, three myeloid cell lines, U‐937, HL‐60 and p39, were found to exhibit unusual C3 deposition or cytolysis. U‐937 possessed DAF and MCP but lacked p18, and about 50% was lysed by treatment with anti‐DAF and anti‐MCP followed by Mg2+‐EGTA‐serum, which caused C3, C5 and C8 deposition. Anti‐DAF evoked similar but less complement (C) deposition and cytolysis while anti‐MCP alone did not, although it enhanced the anti‐DAF‐mediated C deposition and cytolysis. Thus, once the C3 step is overcome, U‐937 is attacked by the late components leading to cytolysis because of the absence of p18. On the other hand, HL60 allowed the deposition of C3 by blocking of either DAF or MCP followed by the Mg2+‐EGTA‐serum treatment. C5, C8 and C9 were subsequently deposited but resulted in no lysis. Lysis of 60% was attained by the additional blocking of p18. Thus, HL60 is poorly protected by C3 and C9 step regulation. Strikingly, extensive C3 deposition occurs on p39 without any antibody treatment, suggestive of the presence of unique alternative pathway activators. However, little cytolysis was induced on p39 even by blocking of all three inhibitors with antibodies. These results suggest that in activation of the alternative pathway on myeloid cells, C3 step is controlled by the inhibitors and alternative pathway activators, and C‐mediated cytolysis is blocked by p18 and additional regulatory mechanisms or factors which assist in protection of nucleated host cells from MAC attack. Susceptibility to homologous C of these cell lines, therefore, reflects relatively low potency of C regulation on their membrane.
Differential in situ expansion and gene expression of CD4+ and CD8+ tumor‐infiltrating lymphocytes following adoptive immunotherapy in a murine tumor model system
Authors: Evans Robert , Duffy Theodore M. , Kamdar Sonya J. 
Published: March 2007

AbstractIn previous reports, we demonstrated that adoptively transferred T cells homed to the tumor site (among other sites) and that amplification of immune responses occurred in situ leading to the generation of cytotoxic CD8+ tumor‐infiltrating lymphocytes (TIL) and macrophages. The present report extends these findings and shows that following adoptive immunotherapy (AIT) of mice bearing the immunogenic transplanted methylcholanthrene‐induced rhabdomyosarcoma (MCA/76‐9) there was a differential expansion of CD4+ and CD8+ TIL, the numbers peaking on days 6 and 8, respectively. At this time, CD8+ TIL accounted for the majority of Thy‐1+ cells. Northern analyses of RNA extracted from positively selected (by panning) Thy‐1+, CD8+ and CD4+ TIL isolated 8 days after AIT indicated the following: in five separate experiments, CD4+ cells expressed three‐ to sixfold more interleukin (IL)2 mRNA and six‐ to eightfold more IL6 mRNA than CD8+ cells, while CD8+ TIL expressed three‐ to sixfold more IL 2 receptor (IL 2R) mRNA and four‐to sixfold more interferon‐γ mRNA than CD4+ cells. TIL cultured in 10% fetal bovine serum failed to release IL2 over a 24‐h period, whereas both IL6 and interferon‐γ activities were demonstrable. The level of IL2R mRNA expression was reflected by a vigorous proliferative response of CD8+ TIL to exogenous recombinant IL2 and only a low response by CD4+ cells suggesting that most of the CD4+ TIL were in the resting stage. This was confirmed when it was shown that the incubation of panned CD4+ TIL with IL2 supplemented with irradiated spleen cells and “spent” 76‐9 tumor culture supernatant (as a source of antigen) induced expansion of TIL resulting in a population consisting of >90% CD4+ TIL. The overall data suggest that the relatively deactivated state of the CD4+ TIL at this particular time reflects the status of the rejection process in terms of the absence or low concentration of stimulating tumor‐associated antigen.
Polymorphisms and haplotypes in the human immunoglobulin x locus
Authors: Pargent Walter , Schäble Karlheinz F. , Zachau Hans G. 
Published: March 2007

AbstractBy comparing the restriction patterns of the DNA from 23 unrelated individuals 16 polymorphisms were defined which allowed us to differentiate between the duplicated copies Op, Ap, Lp and Od, Ad, Ld of the x locus (p for the Cx proximal, d for the distal copy). Some of these duplication‐differentiating polymorphisms or DDP revealed also allelic differences between individuals; they are therefore restriction fragment length polymorphism (RFLP) markers at the same time. Three RFLP in the single copy B‐Jx‐Cx region were included into the study. Three basic haplotypes were derived from the combined genotype data, haplotypes N, G and 11. The latter haplotype in which the whole distal copy of the x locus is missing was found three times among the 46 haploid genomes studied. The genotypes of the family members of an individual who is homozygous for haplotype 11 are consistent with Mendelian inheritance. Haplotypes N and G are distinguished from each other by eight RFLP markers. Six additional haplotypes, which were found in one or several individuals each, can be derived from the basic haplotypes N and G by hypothetical recombination and/or mutation events.
The sgp‐60 mlecule is linked to the plasma membrane via a glycosylphosphatidylinositol anchor
Authors: Cabrero Jesús González , Reiser Hans 
Published: March 2007

AbstractWe have recently identified a novel murine glycoprotein termed sgp‐60, which is expressed on the cell surface of T and B lymphocytes. Because of the profound modulatory effects of sgp‐60 on activation through the T cell receptor/CD3 complex, we have examined the membrane attachment domain of the molecule. sgp‐60 is not expressed on the surface of variants of a T‐T hybridoma cell line that are defective in glycosylphosphatidylinositol (GPI) anchor biosynthesis. In wild‐type but not in mutant cells, sgp‐60 can be labeled with palmitic acid. Furthermore, the molecule can be removed from the cell surface of both T and B lymphocytes by enzymatic digestion with a phosphatidylinositol‐specific phospholipase C. We conclude that the sgp‐60 molecule is linked to the plasma membrane via a GPI anchor.
Characterization of specific T helper cell activity in mice bearing alloantigenic tumors in the anterior chamber of the eye
Authors: Bando Yasuharu , Ksander Bruce R. , Streilein J. Wayne 
Published: March 2007

AbstractP815 tumor cells injected in the anterior chamber (AC) of eyes of BALB/c mice elicit anterior chamber‐associated immune deviation (ACAID) whereby delayed‐type hypersensitivity (DTH) responses to the tumor‐associated antigens are suppressed, precursors of cytotoxic T cells are clonally expanded but not Triminally differentiated, and levels of tumor‐specific serum antibodies are elevated. These results imply the presence of unique helper T(Th) cell functions in these animals. To identify and describe these cells, we first determined the presence of antigen‐activated lymphocytes in AC tumor‐bearing mice, as well as mice that received tumor cells subconjunctivally (SC), as measured by prolifer‐ative responses of lymphocytes from draining lymph nodes and spleens. In addition, we examined the lymphokine secretion profiles [interleukin (IL) 2, IL4] of antigen‐responsive lymph node and spleen cells in limiting dilution analysis. We found that lymphoid organs of mice primed by the SC route contained high frequencies of antigen‐reactive CD4+ cells that secreted IL2 only, or IL2 plus IL4. In addition, IL2‐secreting CD8+ cells were found. Alternatively, the lymphoid organs of mice receiving AC inoculations of P815 cells contained CD4+ as well as CD8+ cells that secreted IL2 after antigen stimulation. However, no IL4‐secreting cells were found. According to a recent model of differentiation of CD4+ T cells, precursors of Th cells (that secrete IL2 alone) differentiate into Th0 cells that can secrete IL2, IL4 and IFN‐γ. These cells further differentiate into Th1 cells and Th2 cells that secrete IL2 or IL4, respectively. We interpret the absence of IL4‐secreting CD4+ cells in AC tumor bearing mice to mean that in these mice precursor Th cells are unable/prevented from differentiating into Th0 cells.
Regulation of interleukin 2 production, interleukin 2 mRNA expression and intracellular glutathione levels in ex vivo derived T lymphocytes by lactate
Authors: Roth Steffen , Droge Wulf 
Published: March 2007

AbstractThe concentration of L‐lactate in the blood plasma of higher vertebrates is about 1 mM but can be as high as 30 mM under certain physiological and pathological conditions or in the vicinity of glycolytically active cells including macrophages. Here we report that high but physiologically relevant concentrations of lactate increase the expression of interleukin 2 (IL 2)‐specific mRNA and the production of IL2 activity in cultures of mitogenically stimulated T cells. Lactate supports IL 2 production most effectively if added 0–8 h after T cell stimulation and only in cultures of CD4+ but not of CD8+ T cells. In contrast to the DNA synthesis activity in these cell cultures, IL 2 production is not augmented but rather inhibited by glutathione (GSH). Lactate causes a reduction of intracellular GSH levels, and lactate‐containing cultures require accordingly higher extracellular cysteine concentrations than control cultures to achieve similar intracellular GSH levels. In view of the strong variations of extracellular lactate concentrations In vivo, our experiments suggest that lactate may be part of a previously unknown mechanism by which the metabolic microenvironment modulates gene expression in T cells.
Apoptosis is associated with the extensive B cell death in the sheep ileal Peyer's patch and the chicken bursa of Fabricius: A possible role in B cell selection
Authors: Motyka Bruce , Reynolds John D. 
Published: March 2007

AbstractThe ileal Peyer's patch (PP) and the bursa of Fabricius have major roles in populating the B cell system in sheep and chickens, respectively. These tissues contain > 90% B cells and possess a massive proliferation index with > 5% of B cells entering mitosis per hour. Paradoxically, almost all of the B cells produced in these sites rapidly die in situ. Here we show that the extensive B cell death occurring in the ileal PP and bursa is associated with apoptosis. Gel electrophoresis of ileal PP cell DNA from 7–14 week‐old lambs and bursal cell DNA from 4‐week‐old chickens demonstrated a laddering of DNA in multiples of approximately 200 bp, a pattern indicative of apoptosis. In sheep, the intensity of the laddering pattern seen after agarose gel electrophoresis was always greater with ileal PP cell DNA compared with thymocyte DNA, and usually greater than jejunal PP cell DNA. Likewise, DNA isolated from chicken bursal cells and mouse PP cells always exhibited a more intense laddering pattern than chicken or mouse thymocytes, respectively. When placed in culture ileal PP cells died rapidly < 40% viable cells were recovered after 24 h. Within 6 h of culture many ileal PP cells exhibited an apoptotic appearance in that they contained condensed chromatin and fragmented nuclei. Moreover, < 55% of total cellular DNA was fragmented. Compared with thymocytes, ileal PP cells underwent DNA fragmentation to a much greater extent and with a faster time course in short‐term culture. We propose that cell death by apoptosis may make an important contribution to B cell development in the lamb ileal PP and the chicken bursa. Apoptosis may provide a mechanism for the diversification of the B cell immune repertoire and/or the selection of non‐self reactive B cells.
The tyrosine kinase activity of p56lck is increased in human T cells activated via CD2
Authors: Danielian Silvia , Fagard Remi , Alcover Andrés , Acuto Oreste , Fischer Siegmund 
Published: March 2007

AbstractAn early biochemical event associated with T cell activation is tyrosine phosphorylation. We have previously shown that p56lck, a lymphocyte‐specific protein tyrosine kinase, is hyperphosphorylated on serine and tyrosine residues 15 minutes after activation via CD2 with a concomitant shift to a higher molecular mass. We now demonstrate that the tyrosine kinase activity of p56lck is increased within seconds following CD2 triggering. This activity decreases thereafter correlating with the appearance of changes in phosphorylation previously described. These results suggest that p56lck may play an important role in the CD2 activation pathway.
Evidence for idiotypic sharing between conventional and naturally activated B cells
Authors: Song Charles H. , Calandra Gertrudis B. , Miller Alexander , Sercarz Eli E. , Keller Margaret A. 
Published: March 2007

AbstractIn the primary immune response to hen egg‐white lysozyme (HEL), approximately 50% of the primary anti‐HEL antibody‐forming cells (AFC) express IdXE, an idiotype absent from the secondary response. Spontaneous IgM enzyme‐linked immunosorbent assay (ELISA)‐AFC in spleen cells from naive A/J mice were analyzed for the occurrence of IdXE by use of two affinity‐purified rabbit antisera, R213 and R8, each raised against a different primary IdXE+, anti‐HEL mAb. Two ELISA‐AFC assay methods were used: direct coating of immunoplates with R213 or development of IgM‐producing ELISA‐AFC with biotinylated R8. From ages 7 days until 6 months, 10–20% of spontaneous IgM AFC were found to be IdXE+. IdXE+ anti‐HEL IgG1 monoclonal antibodies, 2F4 or 3C11 (100 μg/ml), completely inhibited binding of biotinylated R8 (0.5 μg/ml) to spontaneous IgM‐AFC while IdXE−, anti‐HEL IgG1, 5E11 and 2C7, showed no significant inhibition. Greater than 90% of IdXE+ spontaneous IgM‐AFC were not HEL specific. We conclude that a dominant set of idiotopes found in a conventional antigen‐driven immune response can also play a major role in the spontaneously activated B cell repertoire. Our data argue against a bifurcation of the immune system into a compartment of idiotypic network‐related cells and an independent set of non‐network cells subject to antigenic stimulation.
A quantitative assay of peptide‐dependent class I assembly
Authors: Elvin John , Cerundolo Vincenzo , Elliott Timothy , Townsend Alain 
Published: March 2007

AbstractWe have developed a quantitive assay for the measurement of class I assembly induced by peptide. We have applied this assay to H‐2Db, Kb and HLA‐A2.1 with a panel of 49 overlapping peptides derived from HIV‐1 gag protein. We find that the effects of peptide on assembly form a continuous distribution. By defining positives as those that increase the concentration of folded heavy chains more than three standard deviations from the control we show that 7/48 bind A2.1, 11/49 bind Db and 7/47 bind Kb. The assembly assay contrasts with solid‐phase assays in being more discriminating (fewer peptides binding any given class I molecule), and showing less overlap in the patterns of peptides bound by the three class I molecules.
CD3+ T cells in severe combined immunodeficiency (scid) mice. IV. Graft‐vs. ‐host resistance of H‐2d scid mice to intravenous injection of allogeneic H‐2b (C57BL/6) spleen cells
Authors: Claesson Mogens H. , Rudolphi Angelika , Tscherning Thomas , Reimann Jörg 
Published: March 2007

AbstractIntraperitoneal injection of 2 × 107 nonfractionated spleen cells (SC) from C57BL/6 (B6, H‐2b) mice into completely allogeneic immunodeficient H‐2d scid mice induced clinical and histological signs of acute graft‐vs.‐host disease (GVHD), with all transplanted severe combined immunodeficiency (scid) mice dying in the 3rd week post‐transfer. In contrast four out of five scid mice survived for > 7 weeks after intravenous (i.v.) injections of equal numbers of B6 SC. Intravenously allotransplanted scid mice analyzed in the 8th week post‐transfer had engrafted donor‐type CD4+ and CD8+ T cells in the spleens but showed no clinical or histological evidence of GVHD. i.v. injection of 107 or 106O B6 SC engrafted allogeneic T cells in spleens of scid recipients; in contrast, i.v. injection of 105 nonfractionated B6 SC or 3 × 105 cell sorter‐purified, naive or anti‐H‐2d‐primed splenic CD4+ or CD8+ B6 T cells led to rejection by young scid recipient mice. B6 T cells engrafted into spleens of scid mice after i.v. injection showed proliferative anti‐host alloreactivity in vitro. No cytotoxic reactivity against host‐type alloantigens was found in standard 4‐h 51Cr‐release assays. These data demonstrate that allogeneic T cells injected i.v. into immunodeficient scid mice are partially tolerized against host‐type alloantigens.
Homotypic aggregation of human cell lines by HLA class II‐, class Ia‐ and HLA‐G‐specific monoclonal antibodies
Authors: Ødum Niels , Ledbetter Jeffrey A. , Martin Paul , Geraghty Daniel , Tsu Theta , Hansen John A. , Gladstone Paul 
Published: March 2007

AbstractMajor histocompatibility complex (MHC) class II molecules have been implicated in cell adhesion in two ways. In addition to the well‐established role of class II antigens in low‐affinity adhesion provided by interactions between class II and CD4, recent data indicated that class II may also induce adhesion between T and B cells by activating the CD18/CD11a (LFA‐1) adhesion pathway. Here we report that monoclonal antibodies (mAb) against HLA‐DR (L243, p4.1, HB10a, VI15) and certain broad class II reacting mAb (TU35, TU39), but not anti‐DQ (TU22, Leu‐10) mAb, induced homotypic aggregation of human class II‐positive monocytic (1937) and T leukemic (HUT78) tumor cell lines and Epstein‐Barr virus (EBV) transformed B‐lymphoid cell lines (EBV‐LCL). Class II‐negative cell lines (U‐937 and the EBV‐LCL mutant line 616) were not induced to aggregate. An HLA‐G‐transfected EBV‐LCL, 221‐AGN, but not the class I‐negative parental line, 221, showed homotypic aggregation in response to an HLA‐G specific mAb (87G) and a broad reacting class I‐specific mAb (IOT2). Both cell lines responded with aggregation to anti‐class II mAb (TU35). The anti‐class I mAb, W6/32, had no effect on all cell lines tested and two anti‐β2‐microglobulin mAb had variable, weak effects. The aggregation response was an active, temperature‐sensitive process which was almost totally abrogated by azide and by cytochalasins B and E, but unaffected by colchicine, EDTA, aphidicolin, actinomycin D and protein tyrosine kinase inhibitors (genistein, herbimycin A). Serine/threonine protein kinase inhibitors (staurosporin, H7) partly inhibited the aggregation responses. There was no strict correlation between induction of aggregation and epitope density. FcR were not involved in the aggregation response, since F(ab')2 fragments of anti‐DR mAb, L243, were as effective as the whole antibody. The aggregation was not influenced by mAb against accessory molecules previously shown to be involved directly or indirectly in homotypic aggregation [CD11a (LFA‐1)/CD18/CD54 (ICAM‐1), CD58 (LFA‐3)/CD2, BB1/CD28, CD43, and CD44]. In conclusion, these data provide further evidence that HLA molecules are implicated in a novel, cellular aggregation phenomenon involving the cytoskeleton.
Synovial fluid‐derived Yersinia‐reactive T cells responding to human 65‐kDa heat‐shock protein and heat‐stressed antigen‐presenting cells
Authors: Hermann Elisabeth , Lohse Ansgar W. , Van Der Zee Ruurd , Van Eden Willem , Mayet Werner J. , Probst Peter , Poralla Thomas , zum Büschenfelde Karl‐Hermann Meyer , Fleischer Bernhard 
Published: March 2007

AbstractHumoral and cellular immune reactions to heat‐shock proteins have been implicated in the pathogenesis of arthritis. Heat‐shock proteins occur in bacteria as well as all eukaryotes and have been highly conserved during evolution. Cross‐reactivity between bacterial and human heat‐shock proteins induced at the site of inflammation may underlie the pathogenesis of some forms of arthritis. In order to test this hypothesis, we raised and cloned a Yersinia‐specific T cell line from the synovial fluid lymphocytes of a patient with Yesinia‐induced reactive arthritis. From this line we obtained a CD4+ T cell clone that proliferated in response to Yersinia antigens and both to the mycobacterial and the human 65‐kDa heat‐shock protein. This T cell clone also proliferated in response to autologous heat‐stressed antigen‐presenting cells as well as to synovial fluid mononuclear cells from the inflamed joint, thus showing true autoreactivity against endogenously synthetized self‐antigen. These results demonstrate the induction of an autoimmune T cell response by a natural bacterial infection and support the important role of heat‐shock proteins in the pathogenesis of immune‐mediated arthritis.