bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased expression of CD80, CD86 and CD70 on T cells from HIV‐infected individuals upon activation in vitro: regulation by CD4+ T cells
Authors: Wolthers Katja C. , Otto Sigrid A. , Lens Susanne M. A. , Kolbach Dinanda N. , van Lier René A. W. , Miedema Frank , Meyaard Linde 
Published: March 2007

AbstractT cells express CD28 and CD27 which transduce co‐stimulatory signals after interaction with their ligands on antigen‐presenting cells (APC). These ligands, CD80, CD86 and CD70, are also expressed to some extent on activated T cells. Here, we show that in human immunodeficiency virus (HIV)‐infected individuals, CD28 and CD27 expression is decreased on CD8+ T cells. On the other hand, T cell stimulation in vitro induced high CD80, CD86 and CD70 expression on T cells from HIV‐infected individuals. It appeared that an inverted CD4:CD8 T cell ratio could explain this enhanced expression of co‐stimulatory ligands. Indeed, high expression levels of CD80, CD86 and CD70 were found on activated CD8+ T cells from HIV− individuals cultured in the absence of CD4+ T cells. Addition of CD4+ T cells prevented this up‐regulation. However, in HIV‐infected individuals, addition of excess autologous or healthy control CD4+ T cells did not completely counteract up‐regulation of co‐stimulatory ligand expression on CD8+ T cells. Thus, to some extent, CD8+ T cells in HIV‐infected individuals appeared to be refractory to CD4+ T cell‐mediated regulation of ligand expression in vitro. Activated T cells from HIV‐infected individuals and activated CD8+ T cells from healthy controls were able to act as accessory cells in CD3‐induced T cell proliferation, which was dependent on cell‐cell contact. Thus, we showed that T cells from HIV‐infected individuals express enhanced levels of co‐stimulatory ligands upon activation, which provides them with accessory cell properties. Enhanced stimulatory potential of these nonprofessional APC may contribute to persistently high levels of immune activation in HIV infection related to disease progression.
Identification of a tonsil IgD+ B cell subset with phenotypical and functional characteristics of germinal center B cells
Authors: Billian Gisèle , Bella Chantal , Mondière Paul , Defrance Thierry 
Published: March 2007

AbstractWe have identified and isolated a subpopulation of IgD+ B cells (IgD+ CD38+ B cells) from human tonsils which expresses the germinal center (GC)‐associated surface markers CD10, CD38, CD75, CD77 and CD95/Fas. The heterogeneity of expression of several markers on IgD+ CD38+ B cells suggests that this population can be further subdivided into two discrete subtypes. On a functional basis, IgD+ CD38+ B cells behave as GC B cells as they rapidly and spontaneously undergo apoptosis in vitro and cannot be stimulated to synthesize DNA upon cross‐linking of the antigen receptor. However, in contrast with most GC B cells, IgD+ CD38+ B cells have not completed Ig class switching since they predominantly secrete IgM following stimulation in vitro and lack surface expression of secondary isotypes. Immunoenzymatic staining performed on tonsil tissue sections revealed that IgD+ CD38+ B cells are located in two distinct histological structures: within the GC of a few classical secondary follicles, in which they appear as scattered cells, and within rare atypical GC, homogeneously constituted of IgD+ B cells. Taken together, our findings indicate that IgD+ CD38+ B cells constitute a novel subset of GC B cells. The possibility that these cells could represent an early stage of the follicular reaction or be generated in response to certain bacterial carbohydrate antigens is discussed.
Expression of an avian CD6 candidate is restricted to αβ T cells, splenic CD8+ γδ T cells and embryonic natural killer cells
Authors: Göbel Thomas W. F. , Chen Chen‐Lo H. , Cooper Max D. 
Published: March 2007

AbstractA candidate avian CD6 homolog is identified by the S3 monoclonal antibody. The S3 antigen exists in a phosphorylated glycoprotein form of 130 kDa and a nonphosphorylated form of 110 kDa. Removal of phosphate groups and N‐linked carbohydrates indicates a 78‐kDa protein core. During thymocyte differentiation, the γδ T cells do not express S3, whereas mature CD4+ and CD8+ cells of αβ lineage acquire S3 antigen. All αβ T cells in the blood and spleen express the S3 antigen at relatively high levels. In contrast, only the CD8+ sub‐population of γδ T cells in the spleen expresses the antigen and neither αβ nor γδ T cells in the intestinal epithelium express the S3 antigen. The S3 antigen is also found on embryonic splenocytes with a phenotypic profile characteristic of avian natural killer cells. The biochemical characteristics and this cellular expression pattern imply that the S3 antigen is the chicken CD6 homolog.
Establishment of tissue‐specific tolerance is driven by regulatory T cells selected by thymic epithelium
Authors: Modigliani Yves , Coutinho Antonio , Pereira Pablo , Le Douarin Nicole , Thomas‐Vaslin Véronique , Burlen‐Defranoux Odile , Salaün Josselyne , Bandeira Antonio 
Published: March 2007

AbstractGrafts of thymic epithelium (TE) rudiments restore T cell development and function in allogeneic athymic mice. These TE chimeras are specifically tolerant to grafts of peripheral tissues (e.g. skin and heart) from the TE donor strain, although they harbor peripheral immunocompetent T cells capable of rejecting those grafts. Initial analysis has shown that TE chimeras also harbor TE‐selected CD4 T lymphocytes that inhibit graft rejection by tissue‐reactive T cells in immunocompetent recipients. Peripheral tolerance in TE chimeras is thus maintained by dominant mechanisms dependent on regulatory CD4 T lymphocytes. Here we show that TE‐selected regulatory T cells recruit nontolerant tissue‐reactive CD4 and CD8 T cells to express similar regulatory functions. Only recent thymic emigrants, but not peripheral resident mature T cells are susceptible to this process of functional education, which also requires exposure to specific antigens and occurs entirely in the periphery. We propose that these mechanisms play a major role in establishing and maintaining natural self tolerance to tissue‐specific antigens.
A novel surface molecule homologous to the p58/p50 family of receptors is selectively expressed on a subset of human natural killer cells and induces both triggering of cell functions and proliferation
Authors: Bottino Cristina , Sivori Simona , Vitale Massimo , Cantoni Claudia , Falco Michela , Pende Daniela , Morelli Luigia , Augugliaro Raffaella , Semenzato Gianpietro , Biassoni Roberto , Moretta Lorenzo , Moretta Alessandro 
Published: March 2007

AbstractHuman natural killer (NK) cells express inhibitory (p58) or activatory (p50) receptors for HLA‐C alleles. Here, we describe a novel member of the p58/p50 family that is expressed by a subset of NK cells in about one third of donors. This molecule, termed p50.3, mediates NK cell triggering as revealed by the induction of intracellular free calcium mobilization, cytokine release and cytotoxicity. In addition, anti‐p50.3 monoclonal antibody (mAb) induced a selective, strong proliferation of p50.3+ NK cells in peripheral blood lymphocytes. Although p50.3 molecules do not appear to display an obvious HLA class I specificity, they are usually coexpressed with known inhibitory receptors for HLA class I alleles. mAb‐mediated cross‐linking of these receptors leads to inhibition of the anti‐p50.3 mAb‐induced NK cell activation and proliferation. Surface p50.3 molecules are glycoproteins of ∼ 55–58 kDa which, upon deglycosylation, display a relative molecular mass of 36 kDa, similar to that of deglycosylated (activatory) p50 receptors. Analysis of the two‐dimensional peptide maps of the 50.3 molecules revealed a high homology with the other HLA‐C‐specific p58/p50 receptors. The use of a set of oligodeoxynucleotide primers, previously shown to amplify the activatory (p50) forms of HLA‐C‐specific receptors, consistently amplified in p50.3+ clones a cDNA sequence termed KKA3. This sequence belongs to the p58/p50 multigene family, that encodes for a transmembrane protein specifically stained by anti‐p50.3 mAb in cell transfectants. Similar to p50 molecules, the KKA3‐encoded molecules are characterized by two extracellular immunoglobulin‐like domains, by the presence of a lysine in the transmembrane region and a short (39 amino acids) cytoplasmic tail which does not contain immune receptor tyrosine‐based activation motifs (ITAM)‐like sequences.
A biological function for the XP motif within the N terminus of major histocompatibility complex class II‐associated peptides
Authors: Breloer Minka , Ehrlich Svenja , Fleischer Bernhard , von Bonin Arne 
Published: March 2007

AbstractA high proportion (up to 30%) of major histocompatibility complex (MHC) class II‐bound peptides in the mouse and humans contains a proline residue at the N‐terminal penultimate position (XP motif). We used a set of ovalbumin (OVA)‐specific and hen egg lysozyme (HEL)‐specific T cell hybridomas and asked whether the XP motif in MHC class II‐associated peptides might influence the stimulation of T cells. We created N‐terminally substituted variants of OVA323–339, an H2‐Ad restricted OVA epitope and of HEL50–63, a dominant epitope in the context of H2‐Ak. Our results show that the N‐terminal sequence of MHC class II‐bound peptides has a strong impact for the overall stimulation of specific T cells. Proline at the N terminus of antigenic peptides, in contrast to other amino acids, is tolerated or even enhances the recognition of MHC class II‐bound peptides significantly.
Distinct mechanisms mediate SHC association with the activated and resting B cell antigen receptor
Authors: D'Ambrosio Daniele , Hippen Keli L. , Cambier John C. 
Published: March 2007

AbstractLigation of the B cell antigen receptor (BCR) complex initiates tyrosine phosphorylation of the receptor's transducer components, Ig‐α and Ig‐β and tyrosine kinase‐dependent accumulation of GTP‐bound, activated p21ras. The mechanism of receptor coupling to p21ras activation and the roles of Ig‐α and Ig‐β are unknown. The results reported here indicate that the resting, nonphosphorylated BCR associates with the Grb‐2/Sos‐linker SHC via the Ig‐α immunoreceptor‐based tyrosine activation motif (ITAM). Ig‐α specificity of this interaction is determined by the sequence DCSM found in Ig‐α, but not Ig‐β. Tyrosine phosphorylation of Ig‐α and Ig‐β ITAM allows recruitment of SHC, which now binds directly to both Ig‐α and Ig‐β via a phosphotyrosine/SH2 interaction. In confirmation of recent studies by Saxton et al. (J. Immunol. 1994. 153: 623) receptor ligation leads to tyrosine phosphorylation of SHC and to the formation of a phospho‐SHC/Grb2/Sos complex. In view of previous studies which demonstrated p21ras co‐capping with ligated BCR, the data presented here suggest that Ig‐α/β‐ and SHC tyrosine phosphorylation‐dependent recruitment of the Grb2/Sos complex to the receptor can occur and may provide a mechanism by which the nucleotide exchange activity of Sos could mediate activation of BCR‐localized p21ras.
CD32 expression and signaling is down‐regulated by transforming growth factor‐β1 on human monocytes
Authors: Reterink Thomas J. F. , Klar‐Mohamad Ngaisah , Nibbering Peter H. , Van Es Leendert A. , Daha Mohamed R. 
Published: March 2007

AbstractCD32 (FcγRII) is the most abundantly distributed class of IgG Fc receptors in the human body. In this study, we analyzed the effect of transforming growth factor (TGF)‐β1, a cytokine with strong immunosuppressive function, on the expression and function of CD32 on freshly isolated peripheral blood monocytes and three human monocytic cell lines, U937, THP‐1 and Mono mac‐6. We found that TGF‐β1 down‐regulates CD32 expression on monocytes and all monocytic cell lines in a dose‐ and time‐dependent fashion. A mean down‐regulation of CD32 expression on THP‐1 cells of 54 ± 3.2% after 24 h was found at a concentration of 1 ng/ml TGF‐β1. At the mRNA level, TGF‐β1 induced a twofold down‐regulation of CD32. Cross‐linking of CD32 induced an increase in the concentration of intracellular Ca2+, which was reduced by 50% by TGF‐β1, suggesting a decreased downstream signaling mediated by the receptor.
Triggering through CD40 promotes interleukin‐4‐induced CD23 production and enhanced soluble CD23 release in atopic disease
Authors: Paterson Robin L. K. , Lack Gideon , Domenico Joanne M. , Delespesse Guy , Leung Donald Y. M. , Finkel Terri H. , Gelfand Erwin W. 
Published: March 2007

AbstractThe pathogenesis of atopic disease is closely linked to the overproduction of IgE. CD23 and CD40 are two cellular receptors involved in the regulation of IgE production and both receptors are elevated in atopic disease. We have examined the role of CD40 in the regulation of CD23 and soluble CD23 production in healthy and atopic donors. Triggering of the B cell CD40 receptor directly enhances interleukin (IL)‐4‐mediated up‐regulation of CD23 at both the protein and the mRNA level. When atopic donors were studied, the synergistic effect of CD40 triggering on the IL‐4‐induced up‐regulation of CD23 and soluble CD23 (sCD23) was enhanced and there was a relative skewing toward production of sCD23. These studies implicate the CD40 receptor in the hyperproduction of CD23 and sCD23 in atopic disease and suggest that abnormalities may exist in the cellular pathways leading to sCD23 production.
Nerve growth factor signal transduction in human B lymphocytes is mediated by gp140trk
Authors: Melamed Isaac , Kelleher Colm A. , Franklin Richard A. , Brodie Chaya , Hempstead Barbara , Kaplan David , Gelfand Erwin W. 
Published: March 2007

AbstractNerve growth factor (NGF) plays an important role in the regulation of the immune system. Recent studies from this laboratory demonstrated the presence of functional NGF receptors on human B lymphocytes; in addition, NGF has been shown to enhance B lymphocyte proliferation. NGF caused both concentration‐ and time‐dependent increases in tyrosine phosphorylation of five proteins of 140, 110, 85, 60 and 42 kDa, which were identified as phospholipase C‐γ1, phosphatidylinositol‐3 kinase and mitogen‐activated protein kinase. To elucidate the contribution of the Trk family of tyrosine kinases to the phosphorylation events induced by NGF, we identified gp140trk in human B cells and in human B cell lines. Analysis of specific gp140trk immunoprecipitates indicated that addition of NGF to B cells induced a rapid increase in the tyrosine phosphorylation of gp140trk and inhibition of this phosphorylation prevented the tyrosine phosphorylation of other proteins. These data identify the central role of gp140trk in NGF signaling of human B lymphocytes.
Subepithelial B cells in the human palatine tonsil. II. Functional characterization
Authors: Dono Mariella , Zupo Simona , Augliera Adriano , Burgio Vito L. , Massara Rosanna , Melagrana Andrea , Costa Mauro , Grossi Carlo E. , Chiorazzi Nicholas , Ferrarini Manlio 
Published: March 2007

AbstractThis study investigates the main functional features of subepithelial (SE) B cells and compares them with those of purified germinal center (GC) and follicular mantle (FM) B cells isolated from the same tonsils. Unlike GC B cells, SE B cells failed to produce polyspecific antibodies in vitro; unlike GC B cells, SE B cells expressed high levels of Bcl‐2 and failed to undergo spontaneous apoptosis in vitro. The most striking function of SE B cells was their ability to produce IgM antibodies to T cell‐independent type‐2 (TI‐2) (but not to TI‐1) antigens (Ag). These antibodies could not be detected when both FM and GC B cells were stimulated with TI‐2 Ag in vitro. Moreover, B cells isolated from peripheral blood were unable to mount a response to TI‐2 Ag. The latter finding is consistent with the observation that B cells with the phenotypic features of SE B cells were virtually absent in the peripheral blood and emphasizes the notion that SE B cells belong to a subset of non‐recirculating B cells. SE B cells were by far superior to FM B cells in mixed lymphocyte reaction (MLR) stimulation of allogeneic T cells in vitro, although they were not as efficient as dendritic cells (DC). In order to stimulate T cells efficiently, SE B cells had to be exposed to anti‐μ antibody, a treatment which induced expression of activation markers such as CD80, CD86, CD69 and CD39, usually absent in resting SE B cells. CD80 and CD86 molecules expressed by SE B cells participated in the chain of events required to promote the proliferation of allogeneic T cells as demonstrated by inhibition tests with the appropriate mAb. The expression of CD80 and CD86 by anti‐μ‐treated SE B cells was not, however, the sole explanation for their good antigen presenting capacities since the exposure of FM B cells to anti‐μ antibody also induced expression of these surface structures. Nevertheless, these cells failed to become good MLR stimulators. Collectively, the above data contribute further to the characterization of a distinct subset of tonsillar B cells which resemble, both phenotypically and functionally, the B cells of the splenic marginal zone.
Modulation of integrin‐mediated intercellular adhesion during the interaction of thymocytes with stromal cells expressing VLA‐4 and LFA‐1 ligands
Authors: St‐Pierre Yves , Hugo Patrice , Legault Doris , Tremblay Pierre , Potworowski Edouard F. 
Published: March 2007

AbstractMature peripheral T cells closely regulate their intercellular interactions by modulating integrin adhesion functions. The ability of members of the integrin family to mediate intercellular adhesion is dependent on signals from within the cells (inside‐out signaling) that increase the avidity of integrins for their ligands. These changes in avidity are independent of the quantitative changes on the number of receptors, and there is evidence to suggest that phosphorylation events play a predominant role in the regulation of the avidity state of the integrins. Whether such regulatory mechanisms are operative during T cell development had hitherto been an opened question. In the present work, we have used an in vitro adhesion assay between thymocytes and target cells expressing VLA‐4 and LFA‐1 counter ligands to determine how thymocytes can discriminate between integrin‐specific signals during T cell development. Our findings are that VLA‐4, but not LFA‐1, is constitutively expressed in its high‐avidity state during the early stages of T cell development, and that the high‐avidity state of thymocytes for VCAM‐1‐expressing cells is closely regulated by signaling through protein kinase C and protein tyrosine kinase pathways. At later stages of development, mature thymocytes prior to leaving the thymus turn off both VLA‐4 and LFA‐1 adhesion functions. Our results show that the low‐affinity state of integrins on peripheral mature T cells is established before mature thymocytes leave the thymus. Only when mature T cells recognize antigenic peptides in the context of major histocompatibility complex in the periphery will they turn on the adhesion function of VLA‐4 and/or LFA‐1 integrins.
The p56lck SH2 domain mediates recruitment of CD8/p56lck to the activated T cell receptor/CD3/ζ complex
Authors: Thome Margot , Germain Valérie , Disanto James P. , Acuto Oreste 
Published: March 2007

AbstractThe CD4 or CD8 co‐receptors and the T cell receptor (TCR) are thought to interact with the same antigen‐presenting major histocompatibility complex molecule in a stable ternary complex. Therefore, the TCR and its co‐receptor need to come into close proximity on the surface of the T cell. We have previously shown that the interaction of the p56lck SH2 domain with ζ‐associated, tyrosine phosphorylated ZAP‐70 and Syk kinases leads to an enhanced association of CD4 with TCR/CD3/ζ complex after CD3 stimulation of Jurkat cells. In this report, we analyzed whether a similar mechanism can mediate recruitment of the CD8αβ and CD8αβ isoforms to the TCR. We demonstrate in vivo in association of CD8αα/p56lck with the tyrosine kinase ZAP‐70 after CD3 stimulation of Jurkat cells. A phosphopeptide competing in vitro for the binding of tyrosine phosphorylated proteins to the SH2 domain of p56lck specifically impedes the association of ZAP‐70 with CD8αα/p56lck without affecting the ζ/ZAP‐70 interaction. The same peptide is able to compete for the activation‐dependent association of the CD8αα or CD8αβ isoform with the TCR/CD3/ζ complex. Moreover, co‐precipitation of the TCR with both CD8 isoforms was observed after CD3 stimulation. These findings strongly suggest that the p56lck SH2 domain mediates recruitment of CD8/p56lck to the activated TCR/CD3/ζ complex.
Difference in antigen presentation pathways between cortical and medullary thymic epithelial cells
Authors: Kasai Michiyuki , Hirokawa Katsuiku , Kajino Ki‐Ichi , Ogasawara Kazumasa , Tatsumi Masashi , Hermel Evan , Monaco John J. , Mizuochi Toshiaki 
Published: March 2007

AbstractAntigen presentation by thymic epithelial cells (TEC) to T cells that undergo maturation is one of the major events in the selection of the T cell repertoire. We have already reported that medullary TEC lines (mTEC) established from newborn C57BL/6 (H‐2b) mice are able to present a soluble antigen, ovalbumin (OVA), to OVA‐specific, I‐Ab restricted helper T cell lines but cortical TEC (cTEC) lines are not (Mizuochi, T. et al., J. Exp. Med. 1992. 175: 1601). In this report, to clarify the cause of this difference, we analyzed the biochemical nature as well as the distribution of both major histocompatibility complex (MHC) class II molecules and invariant chains (Ii) in both TEC by immunoprecipitation and laser confocal scanning microscopic analysis, as well as the expression of mRNA encoding H‐2Ma or H‐2Mb. Our results demonstrate that cTEC and mTEC are both able to present peptide antigens to peptide‐specific, I‐Ab‐restricted helper T cell hybridoma and are able to present class II MHC alloantigens to an I‐Ab‐specific T cell line, that mRNA for H‐2Ma and H‐2Mb are expressed in both TEC, that cTEC and mTEC apparently incorporate tetramethylrhodamine isothiocyanate‐labeled OVA in the same manner, and that the SDS‐stable MHC class II molecules, onto which peptides were loaded, are formed in both cTEC and mTEC. However, these molecules were more rapidly degraded in mTEC than in cTEC. In addition, two Ii‐derived polypeptides of approximately 21 kDa and 10 kDa were precipitated by the anti‐class II monoclonal antibody Y3P; 10‐kDa polypeptides were detected in the both TEC, while 21‐kDa polypeptides were detected only in cTEC. Finally, β chains of MHC class II with less sialylated oligosaccharides were precipitated from the cell surface of cTEC. Taken together, these results suggest that there are substantial differences in the antigen‐presenting pathways of cTEC and mTEC, and these difference might be responsible for T cell selection events in the thymus.
Orally induced, peptide‐specific γ/δ TCR+ cells suppress experimental autoimmune uveitis
Authors: Wildner Gerhild , Hünig Thomas , Thurau Stephan R. 
Published: March 2007

AbstractWe investigated the role of γ/δ TCR+ T cells in induction and suppression of the T cell‐mediated disease experimental autoimmune uveitis. Disease induction was studied in Lewis rats perinatally depleted of α/β or γ/δ TCR+ subpopulations. Depletion of α/δ TCR+ cells completely abrogated disease, whereas treatment with anti‐γ/δ antibodies had no influence on onset or intensity of uveitis. However, adoptively transferred γ/δ+ cells from orally tolerized rats could mediate suppression of uveitis in an antigen‐specific fashion. Uveitis induced by a peptide derived from the uveitogenic retinal soluble antigen (S‐Ag) was suppressed by γ/δ+ cells from rats orally tolerized with the same peptide as well as HLA peptide B27PD. This disease ameliorating effect could also be observed when rats were fed with the HLA peptide before immunization with S‐Ag peptide. Transfer of α/β+ T cells from the same donors as well as γ/δ+ or α/β+ cells from animals fed with control peptide had no ameliorating effect.