bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non‐tolerance and differential susceptibility to diabetes in transgenic mice expressing major histocompatibility class II genes on pancreatic β cells
Authors: Götz Jürgen , Eibel Hermann , Köhler Georges 
Published: March 2007

AbstractIn insulin‐dependent diabetes mellitus aberrant expression of major histocompatibility complex (MHC) class II antigens might induce autoimmune destruction of insulin‐producing pancreatic β cells. Here we demonstrate that already the expression of single MHC class II chains (Eαk and Eβb) is sufficient to cause diabetes without affecting β cell morphology and cell numbers. Our transgenes interfere at least in two points of insulin production leading to a severely diabetic phenotype. In one case Eβb expression led to a 10‐30‐fold decrease of mouse insulin mRNA. In another case Eαk expression reduced insulin secretion to background levels. In addition, we also found a patchy distribution of both insulin and Eαk expression, indicating heterogeneity of the β cell population, without the concommittant development of diabetes. Although the transgenic Eαk Eβb MHC class II molecules were expressed on the surface of pancreatic β cells, the transgenic mice did not prove to be tolerant for I‐E antigen. Autoimmune reactions remained absent showing that aberrant MHC class II expression on pancreatic β cells alone is not sufficient for the development of autoimmune diabetes in mice.
Immunoglobulin‐specific T‐B cell interaction. IV. B cell presentation of idiotypic determinant(s) of monoclonal anti‐surface immunoglobulin antibody to idiotope‐recognizing helper T clones
Authors: Rudensky Alexander Y. , Mazel Svetlana M. , Blechman Janna M. , Yurin Vitalij L. 
Published: March 2007

AbstractPreviously, we have demonstrated T‐B cell interactions mediated by T cell recognition of immunoglobulin (Ig) peptide/major histocompatibility complex (MHC) class II complexes derived by the B cell processing of endogenously synthesized Ig molecules. In this report Ig‐specific T‐B cell interaction mediated by B cell presentation of idiotopes (Id) of anti‐sIg antibodies to Id‐specific T cell clones has been studied in Igϰ‐1‐congenic rat strains. A panel of August (RT‐1c; Igϰ‐1a) rat T helper clones specific for Id of syngeneic anti‐Igϰ‐1b C3B9 monoclonal antibody (mAb) has been developed to study IdC3B9 presentation by Igϰ‐1b‐bearing B cells from congenic August.1b (RT‐1c; Igϰ‐1b) rats. Five of seven IdC3B9‐specific T clones responded even at very low concentrations (100‐200 pg/ml) of C3B9 mAb presented by Igϰ‐1b+ B cells. In contrast, the presentation of intact C3B9 mAb by nonspecific antigen‐presenting cells (macrophages, Igϰ‐1a+ B cells, etc.) to IdC3B9‐specific T cells was of low efficiency. The IdC3B9‐specific T cell response to idiotopes of anti‐Igϰ‐1b C3B9 mAb was found to be restricted by RT‐1B molecule and required the processing of intact C3B9 molecule. IdC3B9 epitope recognized by C31 and C5 clones was mapped to the heavy chain of C3B9 mAb. Thus, B cells are able to present peptides related to the V region of anti‐sIg Ab, i.e. Id peptide/MHC class II complexes, to Id‐recognizing T cells. IdC3B9‐presenting B cells are specifically activated both to proliferation and Ig production upon interaction with IdC3B9‐specific T clones. Based on the results of our studies on B cell presnetation of Ig epitopes to T cells a hypothetical model of Ig peptide‐driven T‐B cell interaction has been proposed.
Corynebacterium parvum (Propionibacterium acnes): An inducer of tumor necrosis factor‐α in human peripheral blood mononuclear cells and monocytes in vitro
Authors: Rossol Siegbert , Voth Rita , Brunner Silvia , Müller Werner E. G. , Büttner Matthias , Gallati Harald , zum Büschenfelde Karl‐Hermann Meyer , Hess Georg 
Published: March 2007

AbstractThe present study investigates the potential capacity of the immunostimulant Corynebacterium parvum (C.p.) to induce tumor necrosis factor‐α (TNF‐α) in human peripheral blood mononuclear cells (PBMC) and blood monocytes (BMo) in vitro. Both at the mRNA and protein level, stimulation of PBMC and BMo upon C.p. induces TNF‐α. Compared to the hitherto used TNF‐α inducers in vitro such as Sendai virus, phytohemagglutinin or lipopolysaccharide the C.p. stimulus displayed a threefold stronger induction of TNF‐α production (p < 0.001). Using C.p. as an inducer it was possible to demonstrate that TNF‐α production is regulated by prostaglandin E2; preincubation of the cells with prostaglandin E2 resulted in a reduced C.p.‐mediated TNF‐α production (p < 0.001). Coincubation of interferon‐γ (IFN‐γ) together with C.p. led to an enhanced release of TNF‐α, supporting the assumption that C.p. is a potent TNF‐α inducer. The additive effect of IFN‐γ and TNF‐α on the receptor level was demonstrated by addition of IFN‐γ antibodies to the PBMC cultures. Under these conditions TNF‐α production, stimulated by C.p. and IFN‐γ, was decreased by 30%, compared to the production in assays supplemented with C.p. alone. From these data we conclude that C.p. is a new inducer of TNF‐α in vitro and a useful tool to study TNF‐α production of PBMC and BMo from either healthy donors or from patients.
Cellular requirements for anti‐DNA production induced in mice by immunization with bacterial DNA
Authors: Gilkeson Gary S. , Pritchard Anita J. , Pisetsky David S. 
Published: March 2007

AbstractTo further define DNA immunization as a model for anti‐DNA production, we investigated the cellular requirements for this response in mice immunized with single‐stranded DNA from E. coli. The anti‐DNA responses of genetically immune‐deficient mice and congenic controls were measured by ELISA after immunization with E. coli DNA as complexes with methylated bovine serum albumin in complete Freund's adjuvant. T cell‐deficient BALB/c‐nulnu mice failed to produce IgG anti‐DNA by this protocol despite high backgrounds of IgM anti‐DNA. In contrast, CBA/N mice expressing the xid defect displayed IgG anti‐DNA responses comparable to those of CBA/J mice despite a reduced IgM response; the specificity of CBA/N and CBA/J anti‐DNA antibodies was similar as determined by binding to synthetic DNA and RNA antigens. These results suggest that the anti‐DNA response stimulated by DNA immunization is dependent on T cells but not the B cell population affected by xid. The intact IgG response of immunized xid mice differs from that of lupus mice bearing xid where this gene defect leads to significant reduction of spontaneous anti‐DNA production.
Molecular cloning of sheep T cell receptor γ and δ chain constant regions: unusual primary structure of γ chain hinge segments
Authors: Hein Wayne R. , Dudler Lisbeth , Marcuz Anne , Grossberger Dario 
Published: March 2007

AbstractThe primary structure of sheep T cell receptor (TcR) γ and δ chain constant (C) regions has been determined by cDNA cloning. A comparison of the nucleotide and deduced amino acid sequences of the sheep chains with known human and mouse sequences shows that the primary structure of the immunoglobulin, transmembrane and cytoplasmic Cγ domains and all of the Cδ region has been substantially conserved. However, the hinge or connector region of sheep γ chains differs significantly from all known TcR chains. Clones representing two different sheep Cγ genes were isolated and both contain additional sequence in this region, making them the longest TcR chains so far identified. The hinge region of both sheep Cγ sequences contains two additional cysteine residues and a motif of five amino acids (TTESP or TTEPP) which has been triplicated in one of the clones. Other repetitive segments of 13–17 amino acids could also be identified suggesting that, as in the human Cγ2 gene, this region of the sheep genes could have arisen from an exon duplication or triplication event. Southern blot analysis of sheep DNA confirmed the presence of one Cδ gene and at least two Cγgenes. A restriction fragment length polymorphism that is probably associated with allelic sequence variation in the sheep Cδ gene was detected in DNA from different animals. Although the essential structure of the γ/δ TcR appears well conserved through evolution, the marked heterogeneity evident in the hinge region of γ chains both within and between species, and particularly the presence of additional cysteine residues in the sheep sequences, may be of structural and functional importance.
Differential peripheral expansion and in vivo antigen reactivity of α/β and γ/δ T cells emigrating from the early fetal lamb thymus
Authors: Hein Wayne R. , Dudler Lisbeth , Morris Bede 
Published: March 2007

AbstractThe concentrations of different lymphocyte subsets in the blood of lambs which had been thymectomized (Tx) in utero between days 67‐75 of fetal gestation were measured at birth and at various intervals during the first year of life. Compared to thymus‐intact (Ti) controls, Tx lambs were severely depleted of both α/β and γ/δ T cells at birth (< 10% of control levels). The majority of the residual α/β T cells present in Tx lambs at birth were CD4+CD8−. As the Tx lambs aged, the concentration of α/β T cells in blood increased steadily to reach levels around 50% of control values. In contrast, the circulating γ/δ T cells did not expand in Tx animals and remained barely detectable throughout the observation period, although these cells accounted for 30%‐60% of the T cells in the blood of Ti lambs. The expansion of α/β but not γ/δ T cells was also reflected in changes in the cellular composition of solid lymphoid organs in Tx lambs. B cell numbers were similar in both groups at birth but Tx lambs were persistently B lymphopenic from 3 weeks of age onwards. The α/β T cells that had expanded in Tx lambs responded to stimulation with bacterial antigens in a way that was qualitatively similar to the response in Ti lambs. By contrast, the few γ/δ T cells in Tx lambs responded abnormally. Our results show that although sheep α/δ and γ/δ T cells are equally thymus dependent during ontogeny, the early fetal thymic emigrants which establish the two T cell lineages in the periphery have strikingly different antigen reactivities and capacities for self‐renewal and expansion.
A private idiotype can become recurrent through genetic recombination and gene(s) unlinked to the Igh locus governs its expression
Authors: Mertens Frederic , Berek Claudia , Andris Fabienne , Willems Fabienne , Brait Maryse , Miller Robert , Riblet Roy J. , Slaoui Moncef , Urbain Jacques 
Published: March 2007

AbstractAny immune response is characterized by its idiotypic profile. Two different kinds of idiotype (Id) have been described. Private Id are restricted to a few individuals from a species while recurrent Id appear in a large majority of individuals from the same species immunized with the same antigen. We describe, in this report, an experimental model whereby a private Id can become recurrent through genetic recombination. The immune response of A mice against the hapten arsonate is characterized by a recurrent Id called cross‐reactive idiotype A (CRIA). A strongly CRI, called CRIA‐like, can be occasionally detected in some BALB/c mice (5% to 10%) immunized with arsonate. Molecular studies show that CRIA and CRIA‐like antibodies have highly homologous D segments and identical light chains. By contrast, their VH segments are vastly dissimilar. We have examined the anti‐arsonate response of inbred strains of mice whose Igh loci are recombinant between those of A/He and BALB/c. Interestingly, we have observed that the CRIA‐like Id which is private in BALB/c becomes recurrent in the AXC‐1 strain which harbors the VH genes from BALB/c, the DH and CH genes from A/He. Structural studies demonstrate that highly homologous, VH, VL and D segments are used in BALB/c and AXC‐1mice. The basis for this differential expression of highly similar genes could be linked to the DH locus. However, F1 mice stemming from the cross between AXC‐1 and BALB/c do not express the Id. The backcross analysis shows that the non‐expression of the Id in F1 mice depends on genes unlinked to the Igh locus.
Control of primary and secondary antibody responses by cytotoxic T lymphocytes specific for a soluble antigen
Authors: Yefenof Eitan , Zehavi‐Feferman Revital , Guy Rina 
Published: March 2007

AbstractBALB/c mice immunized with keyhole limpet hemocyanin (KLH) develop Thy‐1+ and CD8+, KLH‐specific cytotoxic T cells (Tc). Such Tc cells can lyse TNP‐specific B cells activated with TNP‐KLH, but not with TNP‐ovalbumin. Cytotoxicity was inhibited by anti‐H‐2K/D antibodies, but not by anti‐Ia antibodies, suggesting a major histocompatibility complex class I‐restricted killing. Selective enrichment for virgin and memory TNP‐specific B cells revealed that the latter cells were relatively resistant to lysis by KLH‐specific Tc cells. Depletion of CD8+ T cells from cultures of TNP‐specific virgin B cells activated with TNP‐KLH and KLH‐primed T cells, increased the titer of anti‐TNP antibodies in the culture supernatants. This increase was reduced if KLH‐primed CD8+ T cells were added to the culture 1 day before its termination. Anti‐TNP antibody secretion by memory B cells activated in the same manner was not affected by depletion or addition of CD8+ cells. These results suggest that Tc cells are generated following immunization with a soluble antigen which may participate in the down‐regulation of primary B cell responses.
Antigens recognized on a melanoma cell line by autologous cytolytic T lymphocytes are also expressed on freshly collected tumor cells
Authors: Degiovanni Gérard , Hainaut Philippe , Lahaye Thierry , Weynants Patrick , Boon Thierry 
Published: March 2007

AbstractPeripheral blood lymphocytes of a melanoma patient were stimulated in vitro with a permanent cell line derived from the autologous tumor. Stable cytolytic T lymphocyte (CTL) clones were obtained that lysed the melanoma cell line and did not lyse autologous Epstein‐Barr virus‐transformed B lymphocytes or K‐562 cells. These CTL clones were directed against two distinct antigens on the melanoma line. In view of the possibility that these antigens could be culture artefacts, we tested the stimulatory ability of tumor cells that had been freshly collected from metastatic relapses on the CTL clones. A considerable CTL proliferation was observed and it appeared to be specific. We conclude that the antigens recognized by the autologous CTL clones on the permanent melanoma cell line were expressed by the tumor cells in the patient.
Quantitative changes in T cell DNA methylation occur during differentiation and ageing
Authors: Golbus Joseph , Palella Thomas D. , Richardson Bruce C. 
Published: March 2007

AbstractDNA methylation is one of the mechanisms involved in the regulation of developmentally relevant genes. Previous experiments demonstrated that T cells treated with DNA methylation inhibitors reacquire some of the phenotypic and functional characteristics of thymocytes, suggesting that DNA methylation may be involved in regulating some of the changes in gene expression during thymic maturation. To further examine whether changes in DNA methylation occur during T cell differentiation, total DNA deoxymethylcytosine content was compared in human thymocyte subsets and mature T cells. A significant increase in deoxymethylcytosine was found at the end of T cell differentiation which then decreased with age. These results suggest that increased DNA methylation may serve to silence genes following T cell differentiation. The results also raise the possibility that age‐related decreases in T cell DNA methylation may contribute to changes in T cell function occurring in the elderly.
Human breast milk T lymphocytes display the phenotype and functional characteristics of memory T cells
Authors: Bertotto Alberto , Gerli Roberto , Fabietti Giulio , Crupi Silvana , Arcangeli Carla , Scalise Francesco , Vaccaro Renato 
Published: March 2007

AbstractNaive (unsensitized) and memory (antigen‐primed) T cells can be phenotypically distinguished on the basis of the high or low intensity with which they express a number of immunologically relevant lymphocyte membrane antigens, including CD45R, CDw29, UCHL1, LFA‐1, LFA‐3, CD2 and Pgp‐1. Here we report that in contrast to the two major T cell subsets found in the blood, milk T lymphocytes are almost exclusively composed of the one which exhibits the CD45Rlow, CDw29, UCHL1, LFA‐1high memory T cell phenotype. In addition, while milk and autologous blood cells expressed similar levels of CD3 surface antigens, CD2 and ICAM‐1 expression was approximately twofold greater on the milk T lymphocytes. This agrees with the finding that whereas colostrum T cells respond poorly to PHA, they proliferate and produce interferon‐γ normally when stimulated with either the anti‐CD3 or anti‐CD2 monoclonal antibodies. The selective colonization of the mammary gland during lactation by a population of T lymphocytes which displays the phenotype and functional characteristics of memory T cells may be one of the mechanisms whereby the suckling infant benefits from its mother's immunological experience.
Antigen presentation by keratinocytes induces tolerance in human T cells
Authors: Bal Vineeta , McIndoe Angus , Denton Graeme , Hudson David , Lombardi Giovanna , Lamb Jonathan , Lechler Robert 
Published: March 2007

AbstractAntigen recognition by interleukin 2 (IL 2)‐producing T lymphocytes can lead to two distinct outcomes, depending on the nature of the antigen‐presenting cell. Recognition of antigen presented by specialized antigen‐presenting cells leads to T cell activation; in contrast, antigen presentation by cells which lack “accessory function” can lead to a state of specific nonresponsiveness, which is characterized by a failure to produce IL 2. We have shown in this study that co‐culture of an HLA‐DR1/4‐restricted, influenza hemagglutinin‐specific T cell clone with a specific peptide presented by interferon‐γ‐induced DR4‐expressing keratinocytes causes tolerance induction. This effect was DR restricted, in that it required pre‐incubation of the T cell clone with keratinocytes expressing an appropriate DR type (DR 4 Dw14). The induction of T cell tolerance was also antigen specific; no inhibition resulted from pre‐incubation of the clone with an irrelevant peptide. Furthermore cell to cell contact appeared to be necessary, and the addition of supernatant from interferon‐γ‐induced keratinocytes did not cause any inhibition. This phenomenon may have relevance to the immunogenicity of transplanted cultured keratinocytes and to the effects of major histocompatibility complex class II induction on non‐bone marrow‐derived cells. Presentation of tissue‐specific autoantigens by cells such as keratinocytes may provide a mechanism of avoiding, rather than stimulating, autoimmune reactions in the context of a local inflammatory response.
Immunoglobulin light chain transcripts with altered V regions in Burkitt's lymphoma cell lines producing short μ chains
Authors: Cogné Michel , Mounir Samir , Aucouturier Pierre , Preud'homme Jean‐Louis , Nau François , Guglielmi Paul 
Published: March 2007

AbstractThe Burkitt lymphoma cell lines Ly91, Ly47 and Ly66 produce short μ chains in the absence of associated light (L) chains. μ mRNA lack two‐thirds of the variable (V) region due to an alternate splicing event that takes place within V genes. L chain genes were found to be rearranged in these lines and to lead to transcripts with altered V regions. Although these abnormal transcripts displayed specific abnormalities in each cell line, they shared some features, including large deletions involving the V‐J junction. In one cell line, L chain transcripts made up of either VxI subgroup gene Jx3 or VxIV gene‐Jx4 recombination products bore a similar alteration: the donor splice site of the rearranged Jx segment was modified, leading to the alternate use of the donor site of either the leader peptide exon or the next 3′ unrearranged Jx segment.
Binding of toxic shock syndrome toxin‐1 to murine major histocompatibility complex class II molecules
Authors: Scholl Paul R. , Sekaly Rafick‐P. , Diez Ana , Glimcher Laurie H. , Geha Raif S. 
Published: March 2007

AbstractThe staphylococcal exotoxin toxic shock syndrome toxin‐1 (TSST‐1) has potent stimulatory effects on murine and human lymphocytes. This is the consequence of TSST‐1 binding to major histocompatibility complex (MHC) class II molecules and the engagement in a Vβ‐restricted fashion of the T cell receptor by the TSST‐1‐MHC class II complex. Using radioligand and functional assays we have recently shown that TSST‐1 binds to all HLA‐DR (n = 14), HLA‐DQ (n = 2) and HLA‐DP (n = 2) phenotypes tested. In this study, we have examined the ability of murine MHC class II molecules to bind TSST‐1. Specific high‐affinity binding of TSST‐1 was detectable to unfractionated BALB‐c (H‐2d) and C57BL/6 (H‐2b), but not to C3H (H‐2k) spleen cells. The Kd of this binding estimated from Scatchard analysis was in the same nanomolar range as the Kd of binding of TSST‐1 to HLA‐DR. Binding of 125I‐labeled TSST‐1 to BALB/c‐derived B cell lymphoma lines and to L cell transfectants correlated with the expression of I‐A molecules, but not with the expression of I‐E molecules. Furthermore, I‐A+, I‐E− cells but not I‐A−, I‐E+ cells were able to support TSST‐1‐induced T cell proliferation. The binding affinity of TSST‐1 for I‐Ak appears to be much lower than for I‐Ad. L cell transfectants expressing hybrid DRα: I‐E molecules, but not those expressing I‐E: DR1β molecules, could bind TSST‐1 and efficiently support TSST‐1‐induced T cell proliferation. This suggests that minor differences in the highly homologous I‐Eα and DRα chains are critical in determining the affinity of the MHC class II molecule for TSST‐1. These results demonstrate that the binding of TSST‐1 to MHC class II molecules in the mouse, in contrast to humans, is strongly influenced by phenotype. Analysis of the molecular basis of these differences may help to localize staphylococcal exotoxin binding sites on MHC class II molecules.