bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lymphocyte‐mediated inhibition of platelet cytotoxic functions during Hymenoptera venom desensitization: characterization of a suppressive lymphokine
Authors: Tsicopoulos Anne , Tonnel André‐bernard , Vorng Han , Joseph Michel , Wallaert Benoit , Kusnierz Jean‐pierre , Pestel Joël , Capron André 
Published: March 2007

AbstractRecently, it has been shown that platelets, through a receptor for the Fc fragment of IgE, could be specially triggered by venom allergens in hypersensitivity to hymenoptera, generating cytocidal mediators toward Schistosoma mansoni larvae, and oxygen metabolites measured by chemiluminescence. After rush immunotherapy, a depressed platelet response was demonstrated to be associated with the production of lymphokine(s). Here we report the characterization of a factor present in supernatants of antigen‐stimulated T cells from patients after hymenoptera venom desensitization which is able to inhibit platelet cytotoxic functions in a dose‐dependent manner. The optimal inhibition was observed with supernatants obtained after T lymphocyte stimulated with 10−5 μg venom allergen/ml. Once specifically produced the platelet‐suppressive effect of lymphocyte supernatants was not antigen specific. The producing T cell subpopulation was identified as CD8+. This lymphokine had an approximate molecularmass of 25 kDa and a pI of 4.8. It was heat and acid stable and sensitive to trypsin and proteinase K but not to neuraminidase. This platelet inhibitory activity was absorbed by platelet membrane suggesting its binding to a receptor. These properties were very similar to a previously described platelet activity suppressive lymphokine, suggesting the participation of this lymphokine in the mechanisms of rush desensitization.
Analysis of T cell receptor Vβ gene usage in primary mixed lymphocyte reactions : evidence for directive usage by different antigen‐presenting cells and Mls‐like determinants on T cell blasts
Authors: Larsson‐sciard Eva‐lotta , Spetz‐hagberg Anna‐lena , Casrouge Armanda , Kourilsky Philippe 
Published: March 2007

AbstractThe usage of four different T cell receptor (TcR) Vβ gene families within normal, non‐primed T cell populations in response to various types of antigen‐presenting cells (APC) in primary mixed lymphocyte reaction has been studied. We demonstrate that distinct patterns of Vβ gene usage are obtained within a given T cell population in response to different types of APC with the same allo‐H2. When responder T cells are stimulated with one type of allogeneic APC, from various H2‐disparate mice, the same Vβ gene preference is observed. Furthermore, when H2‐ and Mls‐mismatched APC gene used as stimulators, the Mls‐associated Vβ6 and Vβ8.1 gene families are highly elevated in response to both B and T cell blasts from certain Mls‐positive strains. The results demonstrate that different types of allogeneic APC have the capacity to generate biases in TcR Vβ gene usage and imply that functional Mls‐like determinants are presented by T cell blasts. The findings are discussed with respect to TcR‐major histocompatibility complex interactions in allostimulation.
Autoreactive T cells in normal mice: unrestricted recognition of self peptides on dendritic cell I‐A molecules by CD4−CD8− T cell receptor α/β+ T cell clones expressing V β8.1 gene segments
Authors: Seman Michel , Boudaly Sarah , Roger Thierry , Morisset Jean , Pham Ghislaine 
Published: March 2007

AbstractCD4−CD8− double‐negative (DN) and CD4+CD8− T cell clones were derived from splenic precursors resistent to killing by anti‐Thy‐1, ‐CD5, ‐CD4 and ‐CD8 monoclonal antibodies and complement. Both DN and CD4+ clones express functional T cellreceptor (TcR) α/β and exhibit strong autoreactivity in vitro. DN cells can be induced to proliferate by dendritic cells (DC) of all haplotypes tested, although this activation is inhibited by antibodies specific for I‐A determinants expressed on the stimulatory DC. In contrast, CD4+ clones only respond to syngeneic or I‐Ad−compatible DC. Both DN and CD4+ autoreactive clones do not proliferate when cultured with class II+ H‐2d normal or tumor macrophages and B cell lines or with class II‐transfected L cells, suggesting that these cells recognize self peptides only present on the surface ofDC. Despite their phenotype resembling that of immature thymocytes and their inability tointeract directly with B lymphocytes, DN cloned T cells, like CD4+ T cells, exhibit nonspecific helper functions and can induce polyclonal B cell proliferation and differentiation. DN TcR α/β+ peripheral T cells represent, like TcR γ/δ+ lymphocytes, a new T cell subset physiological role whose remains to be defined.
Bovine γ globulin‐specific CD4+ T cells are retained by bovine γ‐globulin‐tolerant mice*
Authors: Burtles Sally S. , Taylor Roger B. , Hooper D. Craig 
Published: March 2007

AbstractImmunological tolerance is an acquired state of antigen‐specific nonresponsiveness which is generally attributed to either the deletion or suppression of tolerogen‐specific T helper cell clones. Unresponsiveness to xenogeneic immunoglobulins can be readily induced and has been extensively studied in order to ascertain the means by whichtolerance is established and maintained. As an absence of reactivity to foreign immunoglobulin has been noted in situations where suppressor cell activity was minimized, this tolerant state has often been ascribed to clonal deletion. The present study demonstrates that bovine γ‐globulin (BGG)‐tolerant mice are unable to generate humoral responses to BGG in vivo and yet harbor BGG‐specific CD4+CD8− T cells which can divide and secrete interleukin 2 when stimulated in vitro. Indeed, the in vitro reactivity to BGG of these cells exceeded that of a similar population of non‐immune cells. This is in direct opposition to the loss of response that would be expected if clonal deletion were operative. The presence of BGG‐specific CD4+ T cells, which appear to be at least partly primed, in mice unresponsive to BGG, indicates that tolerance to BGG is likely to be dependent on unidentified immunoregulatory processes rather than clonal deletion.
Characterization of γ/δ T cell clones isolated from human fetal liverand thymus
Authors: Carding Simon R. , McNamara James G. , Pan Mary , Bottomly Kim 
Published: March 2007

AbstractThe origin and development of T cells bearing γ/δ T cell receptors (TcR) has been extensively studied in the mouse. By contrast, little is known about development patterns and diversity of the human γ/δ T cell lineage. To study therepertoire of human γ/δ+ T cells during T cell ontogeny, wehave isolated clonal populations of γ/δ+ T cells from 14‐week fetal thymus and liver and characterized the molecular compositionof their TcR.The technique of in situ hybridization was used to identify cells expressing TcR genes in fetal liver and thymus. A panel of clones representative of developing T cell populations found in vivo was subsequently isolated from both tissues and clones expressing cell surface γ/δ receptors were identified. Although both the liver‐derived γ/δ+ T cell clone, L2, and the thymus‐derived γ/δ+ T cell clone, T6, had similar cell surface phenotypes, namely CD3+, CD7+, CD45+ and CD8−, their reactivity with anti‐CD2 and ‐CD4 antibodies was different. L2 was CD2high, CD4− whereas T6 was CD2low, CD4low. Both clones possessed effector functions similar to those of adult T cells as demonstrated by the synthesis and secretion of cytokines in response to stimulation through the CD3/TcR complex. Analysis of the TcR composition of the fetal clones showed both clones to possess similar or identical γ chain components, Cγ1, Jγ1/2, Vγ8, and both utilize Vδ gene segments other than Vδ1. This TcR genotype has not been previously reported in the analysis of adult γ/δ+ T cells. Our studies have identified a unique population of human γ/δ+ T cells that may be derived extrathymically and appear to be preferentially and perhaps transiently expressed during fetal life.
Development of cytoplasmic CD3+/T cell receptor‐negative cells in the peripheral lymphoid tissues of chickens
Authors: Pat Bucy R. , Chen Chen‐Io H. , Cooper Max D. 
Published: March 2007

AbstractIn a study of T cell ontogeny using monoclonal antibodies specific for chicken T cellreceptors (TcR) and associated cell surface molecules, we found a subset of lymphocytes that express cytoplasmic CD3 epitopes in the absence of cell surface CD3/TcR complexes. Approximately half of these cells, which were present in the spleen, bursa and intestine of young chick embryos, expressed surface CD8. None expressed CD4, TcR1 (γ/δ), TcR 2 (α/β) or TcR 3 (a third CD3‐associated heterodimer inthe chicken). These cytoplasmic CD3+CD8± cells, tentatively named TcR 0 cells to denote their lack of surface TcR, appeared first in the spleen of 8‐day embryos, 4 days before TcR expression begins in the thymus, and reached a peak frequency of ≈︁ 10% of the splenic cell in 14‐day embryos. The TcR 0 cells were alsopresent in adult birds, where they comprised only about 1% of the CD3+ spleen cells and approximately 40% of the lymphocytes in the intestinal epithelium. We conclude that the avian TcR 0 cells represent a thymus‐independent lineage of lymphocytes which, like natural killer cells in mammals, may play an important role in body defense.
The role of functionally distinct helper T lymphocyte subpopulations in the inductionof human B cell differentiation
Authors: Sleasman John W. , Morimoto Chikao , Schlossman Stuart F. , Tedder Thomas F. 
Published: March 2007

AbstractHuman helper T lymphocytes can be dissected into two functionally distinct subpopulations based on expression of the CD45RA (2H4) or CD45R0 (UCHL‐1) surface antigens. While both subpopulations are able to induce equivalent levels of B cell activation and proliferation, only the CD4+CD45RA− subpopulation is capable of inducing B cell differentiation in pokeweed mitogen (PWM)‐stimulated cultures. To define the mechanism responsible for the dichotomy between induction of proliferation and differentiation by the two CD4+ subpopulations, we examined the abilities of the purified T cell subpopulations to produce lymphokine mRNA following T cell activation. Northern analysis revealed that both subpopulations produced interleukin (IL) 2 and interferon (IFN)‐γ mRNA following PWM activation. The CD4+CD45RA− subpopulation, however, produced higher levels of IFN‐γ mRNA and the CD4+CD45RA+ cells produced higher levels of IL 2 mRNA. Neither subpopulation elaborated detectable mRNA for IL 4, IL 5 or IL 6. Of greatest significance was that the addition of recombinant or T cell‐derived lymphokines could not compensate for the inability of the CD4+CD45RA+ subpopulation to induce B cell differentiation in PWM assays. Direct T‐B cell contact was required for the optimal induction B cell differentiation in these assays, suggesting that CD4+CD45RA+ T cells were deficient in their abilityto directly deliver the T cell‐B cell signals required for B cell differentiation. These results suggest that the differential abililty of the two subpopulations of CD4+ T cells to induce B cell differentiation does not result from differences inlymphokines elaborated, but may result from differences in their abilities to interact directly with B cells to initiate differentiation.
Limited number of immunoglobulin VH regions expressed in the mutant rabbit “Alicia”
Authors: Dipietro Luisa A. , Short Jeffery A. , Zhai Shi Kang , Kelus Andrew S. , Meier Daniel , Knight Katherine L. 
Published: March 2007

AbstractA unique feature of rabbit Ig is the presence of VH region allotypic specificities. In normal rabbits, more than 80% of circulating immunoglobulin molecules bear theVHa allotypic specificities, a1, a2 or a3; the remaining 10% to 20% of immunoglobulin molecules lack VHa allotypic specificities and are designated VHa−. A mutant rabbit designated Alicia, in contrast, has predominantly serumimmunoglobulin molecules that lack the VHa allotypic specificities (Kelus and Weiss, Proc. Natl. Acad. Sci. USA 1986. 83: 4883). To study the nature and molecular complexity of VHa− molecules, we cloned and determined the nucleotide sequence of seven cDNA prepared from splenic RNA of an Alicia rabbit. Six ofthe clones appeared to encode VHa− molecules; the framework regions encoded by these clones were remarkably similar to each other, each having an unusual insertion of four amino acids at position 10. This insertion of four amino acids has beenseen in only 2 of 54 sequenced rabbit VH genes. The similarity of the sequences of the six VHa− clones to each other and their dissimilarity to most other VH genes leads us to suggest that the VHa− molecules in Alicia rabbits are derived predominantly from one or a small number of very similar VH genes. Such preferential utilization of a small number of VH genes may explain the allelic inheritance of VH allotypes.
Defects in signal transduction caused by a T cell receptor β chain substitution
Authors: Reno Toufic A. , Ley Steven , Sugiyama Eiji , Cantagrel Alain , Blumberg Richard , Bonventre Joseph , Terhorst Cox , Yeh Edward T. H. 
Published: March 2007

AbstractAn antigen‐specific T‐T hybridoma was mutagenized with ethylmethane sulfonate and negatively selected by anti‐Ly‐6 antibody‐induced growth inhibition. One of the mutants generated, M4/8, had lost surface expression of a T cell receptor (TcR) Vβ8 epitope detected on the surface of the parental cell line. However, the mutant cell line did express high levels of TcR heterodimer as detected with a pan‐specific anti‐TcR antibody. CD3 ϵ, Ly‐6 and Thy‐1 were expressed at levels similar to the wild‐type parental cell line. Analysis of the surface TcR/CD3 complexes by immunoprecipitation and two‐dimension gel electrophoresis confirmed that the major discernable difference between the wild‐type and mutant TcR/CD3 complexes resided in the TcR β chain. The parental cell line had the potential to express two TcR heterodimers, VαVβ1 and VαVβ8, as determined by Northern blot analysis. Co‐modulation experiments suggested that both types of receptors were expressed. However, the VαVβ8 receptor was the predominant form. In contrast, the mutant M4/8 cell line did not synthesize Vβ8 mRNA and, thus, only the VαVβ1 TcR was synthesized. Despite the normal surface expression of TcR/CD3 complex, the M4/8 mutant cell line did not produce interleukin 2 (IL2) in response to antigen or soluble anti‐CD3 ϵ monoclonal antibody (mAb). Furthermore, it responded poorly to concanavalin A, phytohemagglutinin and anti‐Ly‐6 mAb. Cross‐linking of the stimulatory antibodies partially restored the IL 2 response to anti‐CD3 ϵ or anti‐Ly‐6 to wild‐type levels. Phorbol ester and ionomycin stimulated a full IL 2 response in the M4/8 cell line, demonstrating that the defect in the decreased signaling in the mutant did not result from a defect in the IL2 gene program. In conclusion, these data suggested that the pairing of α/β heterodimer not only determined antigen/MHC specificity but also the signaling efficiency of the TcR/CD3 complex.
T cell receptor Vβ genes expressed by IgG anti‐DNA autoantibody‐inducing T cells in lupus nephritis: Forbidden receptors and double‐negative T cells
Authors: Adams Sharlene , Zordan Tracy , Sainis Krishna , Datta Syamal K. 
Published: March 2007

AbstractIn the (SWR × NZB)F1 (SNF1) model of lupus nephritis, pathogenic variety of IgG anti‐DNA autoantibodies are induced by certain T helper (Th) cells that are either CD4+ or CD4−CD8− (double negative; DN) in phenotype. From the spleens of eight SNF1 mice with lupus nephritis, 149 T cell lines were derived and out of these only 25 lines (≈ 17%) were capable of augmenting the production of pathogenic anti‐DNA autoantibodies. Herein, we analyzed the T cell receptor (TcR) Vβ genes used by 16 such pathogenic autoantibody‐inducing Th cell lines. Twelve of the Th lines were CD4+ and among these five lines expressed Vβ8 (8.2 or 8.3). The Vβ8 gene family is contributed by the NZB parent to the SNF1 mice, since it is absent in the SWR parental strain. Three other CD4+ Th lines expressed Vβ4, another was Vβ2+ and one line with poor autoantibody‐inducing capability expressed Vβ1. Four autoantibody‐inducing Th lines from the SNF1 mice had a DN phenotype and these lines were also autoreactive, proliferating in response to syngeneic spleen cells. Among these DN Th lines, two expressed Vβ6 and one expressed Vβ8.1 TcR. Both of these are forbidden TcR directed against Mls‐1a (Mlsa) autoantigens expressed by the SNF1 mice and such autoreactive T cells should have been deleted during thymic ontogeny. Thus, the DN Th cells of non‐lpr SNF1 mice are different from the DN cells or MRL‐lpr which lack helper activity and do not express forbidden TcR. The spleens of 6 out of 19 nephritic SNF1 animals tested also showed an expansion of forbidden autoreactive TcR+ cells that were mainly DN. Two of these animals expressed high levels of Vβ6 (anti‐Mlsa) and Vβ11 (anti‐I‐E) TcR+ cells, three others had high levels of Vβ11+ cells alone and one animal had an expanded population of Vβ17a+ (anti‐I‐E) cells. The I‐E‐reactive TcR again should have been eliminated in the SNF1 thymus, since they express I‐E molecules contributed by the NZB parent. The SWR parents of SNF1, are I‐E−; moreover, they lack the Vβ11 gene but they express Vβ17a in peripheral T cells. Whereas the NZB parents are I‐E+, they lack a functional Vβ17a gene and they delete mature Vβ11+ T cells. Thus, a combination of MHC class II and TcR genes inherited from the NZB and SWR parents and abnormalities in thymic deletion/selection processes may generate the autoantibody‐inducing Th cells in the SNF1 mice.
Analysis of thymus‐independent type 2 antigen uptake by marginal zone macrophages in thin slices of viable lymphoid tissue in vitro
Authors: Cha David , MacPherson G. Gordon 
Published: March 2007

AbstractThere is evidence to suggest that the B cell population in the marginal zone (MZ) of the spleen is responsible for the antibody response to thymus‐independent type 2 antigens (TI‐2). The macrophage (MΦ) population in the MZ has been shown to take up TI‐2 antigens selectively, and this uptake is potentially important in understanding antigen handling in TI‐2 responses. Uptake has not been studied in vitro because isolation of MZ MΦ completely abrogates uptake. We have adapted a technique for cutting thin slices of viable spleen which retained this MΦ function under in vitro conditions and allowed manipulation of the system. This technique may have widespread application in the study of tissue MΦ which are difficult to isolate. Using this method, we show that MZ MΦ in splenic slices in vitro selectively take up a TI‐2 antigen, in a way apparently identical to that seen in vivo. This is not due to high pinocytic activity by these cells nor to their anatomical location. We provide evidence for a receptor‐mediated uptake system, whose function is sensitive to collagenase. The ligand specificity of the uptake system showed unexpected cross‐reactivity with the mannosyl‐fucosyl receptor with high affinity for mannan, but was not identical to it, and may be indicative of the natural ligands for the TI‐2 antigen uptake system.
Cyclosporin A inhibits rat mast cell activation
Authors: Dráberová L'Ubica 
Published: March 2007

AbstractTo gain further insight into the mechanism of immunosuppression by cyclosporin A (CyA), the effect of CyA on activation of isolated rat mast cells was studied. CyA alone, up to a concentration of 80 μM, had no effect on histamine release from unstimulated mast cells in both calcium‐supplemented and calcium‐free media. However, in the presence of extracellular calcium CyA inhibited, in a dose‐dependent manner (range from 8 nM to 80 μM), histamine release induced by three unrelated secretagogues, the compound 48/80, calcium ionophore A23187 and concanavalin A plus phosphatidylserine. In the absence of extracellular calcium no, or only a marginal, effect of CyA on histamine release induced by the secretagogues was observed. CyA also inhibited the uptake of radiolabeled calcium by the secretagogues‐treated cells. However, CyA did not interfere with the activation‐related early increase in the intracellular free calcium. Thus, CyA‐mediated inhibition of mast cell activation is related to external calcium uptake. These results indicate that rat mast cells belong to the immune cell types whose activity can be modulated by physiologically relevant concentrations of CyA.
The ontogeny of human lymphocyte recirculation: high endothelial cell antigen (HECA‐452) and CD44 homing receptor expression in the development of the immune system
Authors: Horst Eveliene , Meijer Chris J. L. M. , Duijvestijn Adrian M. , Hartwig Nico , Van Der Harten Hans J. , Pals Steven T. 
Published: March 2007

AbstractIn the present report we have studied the expression of a lymphocyte homing receptor, the CD44 antigen, and of HECA‐452, a high endothelial‐specific antigen, during the development of the human immune system. We found that prothymocyte immigrants of the thymus already expressed the CD44 antigen. Similarly, the first peripheral T lymphocytes in fetal lymph nodes, tonsils and gut‐associated lymphoid tissue were also CD44+. Cortical thymocytes and germinal center cells were CD44−. CD44 antigen expression was, thus, not limited to mature recirculating lymphocytes. This suggests that CD44 may not only be involved in recirculation of mature lymphocytes but also in the migration of prothymocytes to their site of maturation, i.e. the thymus. High endothelial venules (HEV) were not demonstrable at the early onset of lymphocyte immigration into the developing lymphoid organs. However, when large‐scale influx of lymphocytes occurred, it paralleled HEV development. HECA‐452 antigen expression preceded the morphological transformation of endothelium into a HEV phenotype. Expression of this antigen therefore, independently reflected the specialized nature of high endothelium. In a patient with complete DiGeorge's syndrome normal HEV developed, indicating that the presence of T lymphocytes is not a requirement for HEV development. Interestingly, a subpopulation of venules located in the thymic medulla near the corticomedullary junction expressed the HECA‐452 antigen. These vessels, which had flat or intermediately high endothelium, are probably involved in lymphocyte migration to the thymus.
Autoantibody specific for a thyroglobulin epitope inducing experimental autoimmune thyroiditis or its anti‐idiotype correlates with the disease
Authors: Tang Haïwen , Bedin Catherine , Texier Béatrice , Charreire Jeannine 
Published: March 2007

AbstractIn order to elucidate the role of anti‐thyroglobulin (Tg) autoantibodies (A‐Ab) in experimental autoimmune thyroiditis (EAT), a kinetic study was conducted in EAT‐susceptible (CBA/J) and non‐susceptible (C57BL/6) strains of mice. From day 0 to 70 post‐Tg immunization, titers of A‐Ab to Tg and to the linear 5‐10‐kDa Tg tryptic fragment inducing EAT as well as anti‐idiotypic A‐Ab representing the internal image of the thyroidogeneic antigen were measured.EAT onset, development and recovery correlate with the presence of two subsets of A‐Ab only in susceptible strains of mice. First, with the presence of anti‐Tg A‐Ab to one determinant borne by the linear 5‐10‐kDa Tg tryptic fragment, and second with the presence of anti‐idiotypic A‐Ab specific for the monoclonal anti‐Tg A‐Ab (3B8G9) paratope which binds to Tg determinant inducing EAT.