bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin‐12 but not interferon‐γ production correlates with induction of T helper type‐1 phenotype in murine candidiasis
Authors: Romani Luigina , Mencacci Antonella , Tonnetti Laura , Spaccapelo Roberta , Cenci Elio , Wolf Stanley , Puccetti Paolo , Bistoni Francesco 
Published: March 2007

AbstractBy means of polymerase chain reaction‐assisted mRNA amplification, we have monitored message levels of interleukin (IL)‐12 in splenic macrophages and of interferon‐γ (IFN‐γ), IL‐4, and IL‐10 in CD4+ and CD8+ T cells using Candida albicans/host combinations that result either in a T helper type‐1 (Th1)‐associated self‐limiting infection (“healer mice”) or in a Th2‐associated progressive disease (“nonhealer mice”). The timing and pattern of message detection did not differ qualitatively by the expression of IFN‐γ or IL‐10 mRNA in CD4+ and CD8+ cells from healer (i.e. PCA‐2 into CD2F1) vs. nonhealer (i.e. CA‐6 into CD2F1 or PCA‐2 into DBA/2) mice. In contrast, IL‐4 mRNA was uniquely expressed by CD4+ cells from nonhealer animals. IL‐12p40 was readily detected in macrophages from healer mice but was detected only early in infection in mice with progressive disease. Cytokine levels were measured in sera, and antigen‐driven cytokine production by CD4+ and CD8+ cells was assessed in vitro, while IFN‐γ‐producing cells were enumerated in CD4− CD8− cell fractions. Overall, our results showed that (i) antigen‐specific secretion of IFN‐γ protein in vitro by CD4+ cells occurred only in healing infection; (ii) IL‐4‐ and IL‐10‐producing CD4+ cells would expand in nonhealer mice in the face of high levels of circulating IFN‐γ, likely released by CD4− CD8− lymphocytes; (iii) a finely regulated IFN‐γ production correlated in the healer mice with IL‐12 mRNA detection, and IL‐12 was required in vitro for yeast‐induced development of IFN‐γ‐producing CD4+ cells. Although the mutually exclusive production of IL‐4/IL‐10 and IFN‐γ by early CD4+ cells may be the major discriminative factor of cure and noncure responses in candidiasis, IL‐12 rather than IFN‐γ production may be an indicator of Th1 differentiation.
Fas‐based lymphocyte‐mediated cytotoxicity against syngeneic activated lymphocytes: A regulatory pathway?
Authors: Vignaux Françoise , Golstein Pierre 
Published: March 2007

AbstractTo investigate the possibility that Fas‐based immune regulation and Fas‐based T cell‐mediated cytotoxicity (F‐CMC) are causally related, we explored the latter in activated lymphocyte populations. These were shown to contain effector cells exerting cytotoxicity via an F‐CMC mechanism which could be differentially triggered by PMA and ionomycin. F‐CMC operated in trans, requiring an lpr (Fas) product on target cells and a gld product on effector cells. Activated lymphocyte populations were also shown to contain F‐CMC target cells. Activated lymphocyte populations thus contained both effector and target F‐CMC cells, which could lyse each other. Fas‐based cytotoxicity can thus lead to the lysis of syngeneic activated lymphocytes, consistent with the possibility of its participation in the down‐regulation of immune responses, and more generally offering a model of socially controlled, direct membrane‐mediated cell death.
CD3 components at the surface of pro‐T cells can mediate pre‐T cell development in vivo
Authors: Jacobs Heinz , Vandeputte Dmitri , Tolkamp Louis , De Vries Evert , Borst Jannie , Berns Anton 
Published: March 2007

AbstractDevelopmentally arrested pro‐T cells (CD4−8−, IL‐2R+, HSA++) of RAG‐1‐deficient mice appear to express low levels of CD3 molecules in the absence of T cell receptor (TcR) chains at their surface, while developmentally arrested pre‐T cells of TcRα‐deficient mice express low levels of a disulfide‐linked TcRβ chain in association with CD3 molecules.Cross‐linking of the CD3 modules on pro‐T cells of RAG‐1−/‐ mice in vivo, with either of two different CD3′‐specific monoclonal antibodies, induces differentiation of these pro‐T cells into pre‐T cells (CD4+8+, IL‐2R−, HSA+), concomitant with a rapid expansion of the thymic T cell compartment, up to 175‐fold within 12 days. The same effects can be produced by introduction of a mutant TcRβ transgene lacking most of the variable domain (ΔV‐TcRβ) into the RAG‐1−/‐ background.These experiments suggest that cross‐linking of the CD3 modules on pro‐T cells mimics the signaling function expected of the pre‐TcR complex, which is found at the surface of pre‐T cells prior to functional TcRa gene rearrangement. The variable domain of the TcRβ chain is apparently not essential for inducing these aspects of T cell development.
Different requirements of ICAM‐1/LFA‐1 adhesion in allorecognition and self‐restricted antigen recognition by class II‐specific T cell clones
Authors: Jaraquemada Dolores , Martí Mercè , Martin Roland , Wagner Annette , MacFarland Henry F. , Rosen‐Bronson Sandra 
Published: March 2007

AbstractWe have analyzed the influence of non‐antigen‐specific interactions between ICAM‐1 and LFA‐1 in target recognition by allospecific and antigen‐specific Tcells at the clonal level, using human and mouse fibroblasts transfected with HLA‐DR1 or DR2 with or without co‐expression of ICAM‐1, as antigen‐presenting cells. The results show a great heterogeneity in the requirements for ICAM‐1/LFA‐1 interactions for antigen‐specific and alloreactive T cell responses and this requirement may depend on the avidity of any particular interaction. The data also show that for most alloreactive clones, ICAM‐1/LFA‐1 adhesion is not sufficient to facilitate efficient T cell recognition of its target molecule. HLA class II recognition by a large proportion of the DR1‐ and DR2‐specific alloreactive clones studied was different for class II molecules expressed on murine or human fibroblasts compared to human lymphoid cells, and was independent of ICAM‐1 expression on the stimulator cells. The inability of some T cell clones to recognize HLA‐class II expressed on non‐lymphoid cells suggests the absence of specific epitopes and could be due to the lack of the relevant peptides, either because they are derived from species‐specific proteins or to differences in processing of endogenous antigen in the transfected stimulator cells.
Distinct involvement of CD45 in antigen receptor signalling in CD4+ and CD8+ primary T cells
Authors: Maroun Christiane R. , Julius Michael 
Published: March 2007

AbstractWe demonstrate that pretreatment of primary CD4+, but not CD8+ T cells with anti‐CD45 inhibits activation signals induced through the T cell receptor for antigen (TCRαβ). Specifically, anti‐TCRαβ‐mediated tyrosine phosphorylation of phospholipase C‐γ1 is inhibited, and this in turn correlates with the inhibition of subsequent Ca2+ mobilization and DNA synthesis. In marked contrast, none of these activation parameters are affected by anti‐CD45 in CD8+ T cells. Perturbation of TCRαβ signalling in CD4+ cells is observed in conditions which do not detectably affect the level of CD45 expression, or its membrane distribution. Further, changes in the intrinsic phosphatase activity of CD45 are not detectable. While anti‐CD45 ablates TCRαβ signalling, anti‐CD3ϵ‐mediated activation is unaffected. This suggests that elements of the antigen receptor complex can be functionally uncoupled, and indicates that the requirements for CD45 in signalling through these two elements are different. The results demonstrate that the involvement of CD45 in coupling TCRαβ to second messenger‐generating pathways is under distinct physical and/or functional constraints in primary CD4+ and CD8+ T cells.
Plastic‐immobilized anti‐μ or anti‐δ antibodies induce apoptosis in mature murine B lymphocytes
Authors: Parry Sarah L. , Holman Mary J. , Hasbold Jhagvaral , Klaus Gerry G. B. 
Published: March 2007

AbstractIt is widely accepted that extensive cross‐linking of surface immunoglobulin (sIg) receptors on mature B cells promotes their activation and progression through the cell cycle. A commonly employed method to maximize receptor cross‐linking via anti‐receptor antibodies is to immobilize them on tissue culture plastic. We show here that immobilizing monoclonal anti‐μ or anti‐δ antibodies, which are mitogenic in solution, on plastic abrogates their capacity to induce DNA synthesis in mature murine B cells, even in the presence of interleukin‐4 (IL‐4). The cells do become abortively activated, as evidenced by up‐regulation of major histocompatibility complex class II antigen levels, but subsequently virtually all of them die, manifesting DNA fragmentation characteristic of apoptosis. The induction of apoptosis is abrogated by the inclusion of either IL‐4 or anti‐CD40 antibodies in the cultures, with the two stimuli acting in concert. We believe that the system represents a polyclonal model of clonal deletion tolerance in mature B cells, such as may be induced under physiological conditions by antigens with repeating epitopes.
A fungal metabolite which inhibits the interaction of CD4 with major histocompatibility complex‐encoded class II molecules
Authors: Gammon Guy , Chandler Glenda , Depledge Paul , Elcock Catherine , Wrigley Stephen , Moore John , Cammarota Giancarlo , Sinigaglia Francesco , Moore Michael 
Published: March 2007

AbstractCD4, a cell‐surface glycoprotein expressed on a subpopulation of T cells, is the receptor for class II molecules of the major histocompatibility complex (MHC II) and a receptor for the envelope glycoprotein (gp 120) of human immunodeficiency virus‐1 (HIV‐1). Screening of microbial metabolites for CD4‐binding activity using an enzyme‐linked immunosorbent assay based on the binding of the CD4‐specific monoclonal antibody (mAb), anti‐Leu3a, identified a family of compounds comprising several novel polyketides. The parent compound (411F, Vinaxanthone) is a C28 molecule probably arising from a dimerization of two C14 polyketide units. It strongly inhibited the interaction of anti‐Leu 3a and that of several other D1/D2 epitope‐specific mAb with CD4, but only weakly inhibited the binding of HIV‐1 gp120. Binding of a representative MHC class II molecule, HLA‐DRB*0401, was also inhibited by 411F with a comparable inhibitory concentration (IC50 = 1 μM). In functional assays 411F inhibited antigen‐induced CD4‐dependent T cell proliferative responses of peripheral blood mononuclear cells. At the clonal level 411F exhibited selectivity in that the compound inhibited peptide‐induced CD4+ T cell proliferative responses but not alloantigen‐induced CD8+ T cell proliferation. It is hypothesized that 411F, a polyanionic compound in aqueous solution at neutral pH, inhibits CD4‐dependent functions by binding over a broad area of the positively charged amino‐terminal D1 and D2 domains implicated in the interaction with MHC II molecules. 411F has the potential for development as an immunosuppressive agent with a novel mechanism of action.
Small CD4+8+TCRlow thymocytes contain precursors of mature T cells
Authors: Swat Wojciech , Boehmer Harald Von , Kisielow Pawel 
Published: March 2007

AbstractTo evaluate directly the developmental potential of cortical CD4+8+ thymocytes, highly purified populations of small, nondividing CD4+8+TCRlow and large, dividing CD4+8+TCRhigh thymocytes from H‐2d mice expressing a transgenic T cell receptor restricted by H‐2Db (major histocompatibility complex class I) molecules were transferred into the thymus of normal, nonirradiated H‐2b recipient mice. The results show that both populations generate CD4−8+ thymocytes under these conditions, thus providing conclusive evidence that small cortical thymocytes do not represent a “dead end” but an important intermediate stage in T cell development.
Orally administered myelin basic protein in neonates primes for immune responses and enhances experimental autoimmune encephalomyelitis in adult animals
Authors: Miller Ariel , Lider Ofer , Abramsky Oded , Weiner Howard L. 
Published: March 2007

AbstractAntigen‐driven tolerance is an effective method for suppression of autoimmune diseases. Adult animals can be tolerized against the induction of experimental autoimmune encephalomyelitis (EAE) by both oral and parenteral administration of myelin basic protein (MBP). We have found that in contrast to previous studies of neonatal tolerance in which parenterally administered autoantigens induced tolerance, the oral administration of MBP in neonatal rats did not result in tolerization to MBP, but instead, primed for immunologic responses. Proliferative responses to MBP and its encephalitogenic epitope were present in animals fed with MBP as neonates and co‐culture of encephalitogenic T cells with cells from neonatal rats fed with MBP were associated with enhanced MBP responses rather than the suppression observed with cells from adult rats fed with MBP. Furthermore, neonates fed with MBP and immunized 6–8 weeks later with MBP in adjuvant to induce EAE revealed enhancement of disease severity, and were not protected from a second attack upon active reinduction of EAE. Subcutaneous injection of soluble MBP into neonates had no effect on EAE induction as adults, whereas intraperitoneal injection of MBP in neonates was associated with marked suppression of disease in adults. Suppression of EAE began to appear in animals fed with MBP at 4 weeks of age, and was similar to oral tolerance in adult animals when animals were fed at 6 weeks of age. These results suggest that immaturity of the immunoregulatory network associated with oral tolerance and sensitization to autoantigens via the gut in the neonatal period may contribute to the pathogenesis of autoimmune diseases.
Inhibition of entire myelin basic protein‐induced experimental autoimmune encephalomyelitis in Lewis rats by major histocompatibility complex class II‐binding competitor peptides
Authors: Wauben Marca H. M. , Kozhich Alexander , Joosten Irma , Schlief Angelique , Boog Claire J. P. , Van Eden Willem 
Published: March 2007

AbstractPrevious studies have shown that major histocompatibility complex (MHC) blockade by competitor peptides with high MHC class II binding affinity can prevent peptide‐induced experimental autoimmune encephalomyelitis (EAE). However, none of these studies addressed the question whether this approach could also be used to prevent EAE induced with a multivalent antigen. In this report we show the effect of competitor peptides co‐immunized during EAE induction with entire guinea pig myelin basic protein (MBP) in Lewis rats. As MHC class II binding competitor peptides we used one nonimmunogenic disease‐nonrelated peptide, and two immunogenic peptides, one EAE‐related and one non‐EAE‐related. The respective efficacy of these three competitor peptides to inhibit MBP‐induced proliferation of an encephalitogenic T cell line in vitro correlated with their respective MHC binding affinity. Co‐immunization of the competitor peptides during disease induction with entire MBP resulted in a competitor concentration‐dependent inhibition of clinical signs of EAE. These results demonstrate that, although polyclonal T cell responses to MBP were not completely inhibited, co‐administration of immunogenic or nonimmunogenic either EAE‐related or non‐EAE‐related MHC class II binding competitor peptides can inhibit the development of EAE induced with entire MBP.
CD3−CD8+ intestinal intraepithelial lymphocytes (IEL) and the extrathymic development of IEL
Authors: Lin Tesu , Matsuzaki Goro , Yoshida Hiroki , Kobayashi Noritada , Kenai Hiroyuki , Omoto Kazuya , Nomoto Kikuo 
Published: March 2007

AbstractPresent evidence suggests that a majority of murine CD3+ intraepithelial intestinal lymphocytes (IEL) are extrathymically derived T cells and that these extrathymically derived IEL phenotypically express the CD8 homodimer (CD8αα). Recently, CD3− IEL have been reported to express the recombination activating gene (RAG‐1), suggesting that precursors to extrathymically derived CD3+CD8+αα IEL exist on the intestinal epithelium. To study in detail whether these CD3− IEL can develop into CD3+CD8+αα IEL, we analyzed the CD3− IEL subset and found that it can be separated into two subsets, namely CD3−CD8− and CD3−CD8+ IEL. We show that (1) CD3−CD8− IEL are mostly small, non‐granular and phenotypically Pgp‐1+ IL‐2R+ B220−, while CD3−CD8+ IEL are mostly large, granular and phenotypically Pgp‐1− IL‐2R+ B220+, (2) CD3−‐CD8+ IEL express the RAG‐1 gene, and (3) CD3−CD8−, CD3−CD8+ and CD3+CD8+αα IEL, respectively, appear sequentially in normal ontogeny and in bone marrow‐reconstituted thymectomized radiation chimeras. In the latter, virtually all CD3+CD8+αα IEL expressed the γδ T cell receptor (TCR), but not the αβ TCR. From this and what is presently known about T cell development, we propose that CD3−CD8+ IEL are an intermediate in extrathymic IEL development and that the development of extrathymically derived IEL occurs at the intestinal epithelium from CD3−CD8− to CD3−CD8+ to CD3+(γδ TCR)CD8+αα.
Flow cytometric determination of cytokines in activated murine T helper lymphocytes: Expression of interleukin‐10 in interferon‐γ and in interleukin‐4‐expressing cells
Authors: Assenmacher Mario , Schmitz Jürgen , Radbruch Andreas 
Published: March 2007

AbstractIn an immune response, effector functions are controlled by T helper (Th) 1 cytokines [interferon‐γ (IFN‐γ), interleukin (IL)‐2 and tumor necrosis factor‐β] and Th 2 cytokines (IL‐4, IL‐5 and IL‐10). Here we analyze by multiparameter immunofluorescence to what extent IL‐2, IL‐4, IL‐5, IL‐10 and IFN‐γ are co‐expressed in individual normal murine Th cells upon activation in vitro with the bacterial superantigen Staphylococcus aureus enterotoxin B, presented in the context of major histocompatibility complex class II. IL‐2 and IFN‐γ are co‐expressed by some, but not by other Th cells. Expression of IL‐4 and IFN‐γ is exclusive. IL‐10 is co‐expressed in individual cells either with IL‐4 or with IFN‐γ. No IL‐5‐expressing cells are detected. While IL‐10‐ and IL‐4‐co‐expressing Th cells correspond to classical Th 2 cells, cells co‐expressing IL‐10 and IFN‐γ could be involved in negative‐feedback regulation of a Th 1 response. Apart from such functional implications, our results show that IL‐2, IL‐4, IL‐5, IL‐10 and IFN‐γ are expressed independently of each other in individual murine Th cells.
Maternal transfer of infectious mouse mammary tumor retroviruses does not depend on clonal deletion of superantigen‐reactive Vβ14+ T cells
Authors: Penninger Josef M. , Wallace Valerie A. , Timms Emma , Mak Tak W. 
Published: March 2007

AbstractFemale C3H/HeJ mice maternally transmit through their milk an infectious mouse mammary tumor retrovirus (MMTV) which causes clonal deletion of T cell receptor (TcR)Vβ14+ T cells reactive to the retroviral superantigen (SAG). To test whether CD4+ or CD8+ T cells are crucial for intestinal infection and maternal transfer of exogenous retroviruses, newborn mice lacking CD4 or CD8 molecules after gene targetting were raised by surrogate C3H/HeJ mothers. In CD8−/− mice, clonal deletion of TcRVβ14+ cells reactive to the SAG from this exogenous MMTV occured with delayed kinetics. Deletion of TcRVβ14+ cells was not observed in CD4−/− mice up to 12 months after exposure to the retrovirus. In both CD4−/− and CD8−/− mice TcRVβ5+ and TcRVβ11+ T cells were deleted in the presence of genomically integrated endogenous MMTV (Mtv), indicating that the lack of SAG‐induced clonal deletion was not due to a general defect in these mutant mouse strains. Although TcRVβ14+ T cells were not deleted in CD4−/− mice, female CD4−/− mice nursed on C3H/HeJ milk maternally transmitted the retrovirus to their offspring, albeit with delayed kinetics. These data demonstrate that CD4+ and CD8+ lymphocytes influence clonal deletion events and that the mechanisms responsible for clonal deletion of SAG‐reactive TcRVβ14+ T cells may be different from mechanisms which allow the mammary tumor virus to enter the mammary gland and complete its infectious cycle.
Thymocyte apoptosis induced by elevated endogenous corticosterone levels
Authors: Gruber Johann , Sgonc Roswitha , Hu Yan Hua , Beug Hartmut , Wick Georg 
Published: March 2007

AbstractA well‐known model of apoptosis is induction in thymocytes by injection of pharmacological doses of exogenous steroids. The aim of this study was to investigate whether this process also occurs under physiological conditions, i.e. by stimulation of endogenous glucocorticoid release, using the chicken as an experimental model. Endogenous glucocorticoid levels can be elevated by immunization with exogenous antigens or by injection of conditioned medium, e.g. supernatant of mitogen‐stimulated spleen cells. This effect is mediated by so‐called glucocorticoid‐increasing factors, and is considered to act as an immunoregulatory principle. Thymocyte DNA of so treated birds showed a typical “ladder” pattern after electrophoresis in a 1.8% agarose gel, and degradation could be prevented by RU 38486. This provides evidence that apoptosis can be induced by elevating endogenous corticosterone levels in vivo. By means of in situ nick translation (ISNT) and simultaneous immunofluorescence tests, it was possible to analyze various thymic subpopulations during apoptosis after treatment with exogenous glucocorticoids. Additionally, using confocal microscopical techniques, apoptosis of the same cells as analyzed by ISNT is shown. The possible role of elevated concentrations of endogenous glucocorticoids in regulating thymocyte cell death and autoimmune diseases is discussed.
T cell subset distribution and B cell hyperreactivity in mice expressing interleukin‐4 under the control of major histocompatibility complex class I regulatory sequences
Authors: Erb Klaus J. , Holtschke Thomas , Muth Kathrin , Horak Ivan , Schimpl Anneliese 
Published: March 2007

AbstractTransgenic mice in which interleukin‐4 (IL‐4) is expressed under the control of the major histocompatibility complex (MHC) class I regulatory sequences show low level expression of IL‐4 in all organs investigated. Several weeks after birth the animals develop thymus hypoplasia with a loss of CD4+CD8+ double‐positive cells and a relative increase in the mature population, especially, and in contrast to previously published lines, the CD4+ single‐positive cells. In the periphery, T lymphocytes eventually decline, CD8+ cells being more strongly affected. Many of the residual T cells exhibit the CD44highMel‐14low phenotype of antigenically experienced T cells. B cells also show an activated phenotype with respect to size, MHC class II and CD23 expression, are more readily stimulated by anti‐μ F(ab′)2 antibodies than are B cells from control littermates, and show a higher spontaneous and antigen‐induced production of IgG1 and IgE.
Human anti‐IgE antibodies by repertoire cloning
Authors: Vogel Monique , Miescher Sylvia , Biaggi Christine , Stadler Beda M. 
Published: March 2007

AbstractAnti‐IgE antibodies have been detected in sera of patients with an allergic disease where they might play a role in the regulation of (Ig)E‐mediated reactions. Using a recombinant phage surface display expression system a combinatorial library of antibody heavy and light chains was constructed from peripheral blood mononuclear cells from an atopic donor immunized with tetanus toxoid. Screening of the library allowed the identification of a large number of phages displaying human monovalent antigen‐binding fragments (Phab) against tetanus toxoid and IgE. Surprisingly, we found a high frequency of Phab against particular IgE myelomas that was comparable to the frequency found for Phab against tetanus toxoid. However, most of these Phab were directed to different idiotypic determinants, depending on the IgE myeloma used for the panning procedure. Nevertheless, two clones were found to have anti‐isotypic specificity and were shown to react specifically with the CH2 domain of the IgE heavy chain.