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G Bismuth

Publications and source records attributed to G Bismuth.

72 records · Page 4Linked to original sources
PubMed1988

Cyclic AMP-mediated alteration of the CD2 activation process in human T lymphocytes. Preferential inhibition of the phosphoinositide cycle-related transduction pathway.

Activation of human T lymphocytes via the CD2 molecule produces an enhanced turnover of phosphatidylinositol (PI) cycle-related phospholipids accompanied by the increased production of diacylglycerol (DG) and phosphorylated derivatives of inositol (IP). In this report we demonstrate that increased levels of intracellular cyclic AMP induced in human T lymphocytes by prostaglandin E2 or dibutyryl cAMP antagonize these early biochemical events of the CD2 activation process. Thus, a substantial inhibition of the CD2-induced increase in 32P-phosphatidic acid and 32P-PI values is observed. In parallel, both the DG production and the IP release triggered by the CD2 signal are strongly reduced contrasting with an almost conserved Ca2+ response. We also report here that cAMP does inhibit the CD2-induced proliferation in a dose-dependent manner while the proliferation generated independently of DG and IP production by a combination of Ca2+ ionophore A23187 and 12-O-tetradecanoylphorbol 13-acetate is not affected. These results therefore suggest that (a) intracellular cAMP levels may participate in the regulation of the PI cycle-related transduction pathway involved in the activation process of human T lymphocytes via the CD2 molecule; (b) the observed cAMP-mediated functional inhibitory effects are mainly related to an alteration of this cellular transduction signal; and (c) considering the putative critical second messenger role in the T cell proliferative response of DG and IP, respectively thought to activate the protein kinase C and to raise the intracellular free Ca2+, the lowering of DG production may be the key event responsible for this cAMP-mediated effect.

Adenylyl Cyclases↗
PubMed1988

Lymphokine mRNA and T cell multireceptor mRNA of the Ig super gene family are reciprocally modulated during human T cell activation.

The expression of genes, implicated in T cell proliferation as well as those coding for the three chains of the T cell receptor (TcR) and for the CD4 and CD8 molecules, has been investigated during activation of various T cell populations maintained in long-term culture. We show that a minimal activation signal, capable of inducing interleukin 2 (IL 2) receptor expression without the expression of IL2 and interferon-gamma, was not associated with a down-regulation of the messengers coding for the T cell multireceptor molecules. In contrast, a strong activation signal via the TcR/CD3 complex or via the CD2 molecule resulted in a reciprocal transient up-regulation of the messengers implicated in T cell proliferation and a down-regulation of the messengers encoding the molecules of the TcR complex of the immunoglobulin super gene family.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1985

Differential effects of monoclonal antibodies anti-L3T4 and anti-LFA1 on the antigen-induced proliferation of T-helper-cell clones: correlation between their susceptibility to inhibition and their affinity for antigen.

Recognition by specific T helper (TH) cells of antigen presented by antigen-presenting cells (APC) involves, in addition to the antigen-specific receptor, non-antigen-specific molecules such as L3T4 and LFA1. In the present study, we analyzed the relationship between the avidity for antigen presented by APC of three TH cell lines and the participation of L3T4 and LFA1 cell surface antigens. We found a correlation between the avidity of TH cells for the complex GAT/Ia on APC measured by two independent assays and the participation of the cell-adhesion molecules L3T4 as measured by the ability of corresponding monoclonal antibody (MAb) to block the antigen-induced proliferation of TH cells. In contrast to the situation found with cytolytic T-lymphocyte (CTL) clones, we also found a differential inhibiting effect of anti-LFA1 MAb on the GAT-specific proliferation of the three TH clones. The results indicate a direct correlation between the inhibitory effects of anti-LFA1 and anti-L3T4 MAb and the affinity of TH cells for the complex formed by antigen and Ia.

Antibodies, Monoclonal↗
PubMed1985

Regulation of interleukin 2 (IL2) receptor expression: IL2 as an inducing signal for the expression of its own receptor on a murine T helper cell line.

The interleukin 2 receptor (IL2R) expression of a terpolymer of L-Glu60, L-Ala30, L-Tyr10 (GAT)-specific T helper (Th) cell line, L14, was studied using two different rat monoclonal antibodies specific for the murine IL2R, 7D4 and 5A2-2. L14 T cells expressed IL2R transiently, but contrary to the general assumption that IL2R expression is maintained only by periodic antigen stimulation, we observed that IL2 itself was able to regulate the level of IL2R on L14 Th lymphocytes. In particular, it was found that L14 T cells, which had not been recently stimulated and which expressed a very low level of high affinity IL2R, could be induced to exhibit a high level of this receptor after exposure to recombinant IL2, in the absence of any specific signal. In contrast, the Th cell line 52.3 used as control could be induced to express high levels of IL2R only after exposure to GAT; nevertheless, IL2 seems to play a critical role in the in vitro survival of the resting state of 52.3 T cells.

Animals↗
PubMed1985

Antigen-specific major histocompatibility complex-restricted helper T cell clones are sufficient to induce unprimed B cells to switch and to secrete IgG and IgA in a primary in vitro polyclonal response.

To investigate the role of helper T (Th) cells in the regulation of the production of the various immunoglobulin (Ig) classes and subclasses, we have used poly (Glu60 Ala30Tyr10) (GAT)-specific, major histocompatibility-complex-restricted Th cell clones to stimulate unprimed B cells. The T cells used in these studies were Thy-1+, Lyt-1+, Lyt-2- and lacked Fc receptor for IgM, IgG and IgA, and the unprimed splenic B cells were selected by the fluorescence-activated cell sorter for their lack of expression of surface (s)IgG and by panning for their lack of expression of sIgA. We have taken advantage of the ability of some antigen-specific major histocompatibility complex (MHC)-restricted Th cell clones to polyclonally activate unprimed B cells in vitro in the presence of high doses of antigen. We have shown that under these conditions, an antigen-specific MHC-restricted Th cell clone is sufficient to induce the switch of sIgG- sIgA- unprimed B cells to IgG and IgA, as well as the expansion of these cells and their differentiation into IgG and IgA-secreting cells. Isotype-specific Th cells thus do not seem to be an absolute requirement for the production of the various IgG subclasses and of IgA.

Animals↗
PubMed1985

LPS and specific T cell responses: interleukin 1 (IL 1)-independent amplification of antigen-specific T helper (TH) cell proliferation.

Lipopolysaccharide (LPS) fraction of endotoxin induces a significant potentiation of the antigen-specific proliferative response of T helper (TH) cell lines. This effect was obtained with LPS from different bacterial sources and reproduced with the lipid A moiety of endotoxin. Purified adherent spleen cells used as antigen-presenting cells (APC) support this LPS-enhanced TH cell proliferation. In addition, the effect of endotoxin on specific TH cell responses was found to be absolutely dependent on the interaction between TH lymphocytes and APC through antigen-specific recognition. Thus, it was not observed in the absence of specific antigen or when monoclonal antibodies against class II MHC products or against L3T4 antigens were used to inhibit the T cell-APC interaction. Similarly, it was found that APC from the B6.CH-2bm12 mutant do not support the LPS-mediated enhancing effect. Furthermore, interleukin 1 (IL 1) appears not to be involved in LPS-mediated enhancement, and this effect is not reproduced by muramyl dipeptide (MDP)-mediated activation of APC.

Adjuvants, Immunologic↗
PubMed1985

Differential requirements for the production by a T helper clone of the lymphokines involved in the induction of polyclonal proliferation and differentiation of unstimulated B lymphocytes.

Antigen-activated T helper (TH) cells secrete into their supernatant various lymphokines that are able to drive B cells to proliferate and to differentiate into Ig-secreting cells. In this report, we compared the production of these two types of activities by a TH clone. We found that B cell proliferating activity was released by TH cells under conditions in which T cell proliferation and the release of the B cell differentiating activity were totally blocked by anti-L3T4 monoclonal antibody GK1.5. The release of these two activities also dissociated during the reversion of T cells to the resting state after activation with antigen. Two weeks after activation, the T cell clone still secreted B cell proliferating activity, but did not secrete B cell differentiating activity. Three to four weeks after activation, neither activity was produced. The data suggest that the genes coding for these two activities are independently regulated in activated T cells. The implications of these observations concerning B lymphocyte development are discussed.

Animals↗
PubMed1984

Poly(Glu60,Ala30,Tyr10) (GAT)-specific T cells do not express B cell public idiotopes but can be primed by monoclonal anti-idiotypic antibodies.

Eight monoclonal anti-idiotypic antibodies directed against public idiotopes have been further characterized: (a) they bind to public idiotopes with a high affinity; (b) they recognize all anti-poly(Glu60,Ala30,Tyr10) (GAT) antibodies as measured by inhibition of the anti-GAT plaque-forming cell response. This has been verified in three strains of mice. These reagents were not able to detect idiotope expression on eight GAT-specific helper T cell lines and clones. This result was obtained by two techniques: (a) idiotope expression at the T cell surface was measured by indirect immunofluorescence using a cell sorter with surface antigens H-2D, Thy-1.2, Lyt-1 and L3T4 as positive controls; (b) after immunoadsorption of [35S] methionine-labeled cellular extracts from two lines, no unique molecule was retained by the HP-idp22 monoclonal anti-idiotypic antibody coupled to Sepharose. Despite these negative results, this antibody was found to prime lymph node cells in vivo, which were able to proliferate specifically in response to GAT. Two T cell lines derived from this lymphocyte population do not express any of the idiotopes tested. These results suggest that monoclonal anti-idiotypic antibodies may be influencing T lymphocyte activity indirectly.

Animals↗
PubMed1984

In vitro induction and expression of interleukin 2 receptor in a clonal T helper cell differentiation model.

Induction and expression of interleukin 2 (IL 2) receptor have been studied using a poly( Glu60 Ala30 Tyr10 ) (GAT)-specific T cell clone of mouse origin. This clone (52-3) has been characterized and it exhibits functional properties of T helper (TH) cells: it leads to a specific anti-DNP response in the presence of DNP-GAT and DNP-primed B cells and it secretes biological activities which can induce polyclonal B cell proliferation and IgM secretion. In vitro this clone mimics the activation stages of normal T lymphocytes and can be obtained under two states of differentiation. depending on the antigen-specific signal provided by antigen-presenting cells (APC). The expression of IL 2 receptor by this clone has been studied by (i) its response to IL 2, (ii) its capacity to absorb IL 2 bioactivity, and (iii) its reactivity with monoclonal antibody 7D4 specific for mouse IL 2 receptor. All the results indicate that the unstimulated state does not express the IL 2 receptor while the activated state does. Clone 52-3 has been compared with clone 14-1.6 that derives from a TH cell line and expresses the IL 2 receptor constitutively. 52-3 offers a good experimental model for studying in vitro, in a clonal TH cell population, the detailed mechanism of IL 2 receptor induction.

Animals↗
PubMed1984

Antigen-specific helper T-cell clone supernatant is sufficient to induce both polyclonal proliferation and differentiation of small resting B lymphocytes.

Gradient-purified resting B lymphocytes can be polyclonally stimulated by antigen-specific major histocompatibility complex (MHC)-restricted helper T lymphocytes as well as by antigen-activated helper T-cell supernatant. In contrast to what has been described so far, we show that helper T-cell supernatant (in the absence of any other added stimulus, such as that provided by anti-mu antibodies) is sufficient to induce both proliferation of resting B cells and their differentiation into IgM-secreting cells. The stimulation induced by the helper T-cell supernatant takes place in serum-free medium and is not MHC-restricted. Our findings strongly support the existence of a B-cell activating factor acting on the resting B cell and causing it to enter the G1 phase of the cell cycle in a MHC-unrestricted manner.

Animals↗
PubMed1984

The use of monoclonal anti-idiotypic antibodies for studying antigen-specific T and B cell receptors.

Eight syngeneic HP-id specific for anti-GAT antibodies are tested for their capacity to detect idiotypes on GAT-specific T cell lines. Their affinity constants are between 5 X 10(-7) and 10(-8) molar-1 which permit significant binding analysis. They detect idiotopes expressed in anti-GAT sera from all the strains of mice tested and by 14 BALB/c HP-GAT. In addition, the distribution of the corresponding idiotopes among all allogeneic HP-GAT allow the identification of two groups of idiotopes. Some idiotopes are expressed by a minority of HP-GAT; the other idiotopes are expressed by all of them. Nevertheless, in spite of the broad molecular and genetic distribution of these idiotopes on anti-GAT antibodies, they are not expressed by three GAT-specific T cell lines from different genetic origins.

Animals↗
PubMed1983

Idiotype expression and fine specificity of Glu60Ala30Tyr10-specific T proliferating cells.

The fine specificity of anti-Glu60Ala30Tyr10 (GAT) and anti-Glu60Ala40 (GA) proliferating cells was studied. T cells primed with GAT proliferate both to GAT and GA and GA-primed T cells proliferate also to GA and GAT. This cross-reactivity was unexpected given the results previously reported on the fine specificity of anti-GAT antibodies. The effect on the proliferation of BALB/c lymph node cells (LNC) of a syngeneic anti-idiotypic serum, prepared in BALB/c against anti-GAT antibodies, was studied. Two major points are made in this paper: (i) the in vitro addition of the anti-idiotypic serum in cultures containing GAT-primed LNC and GAT enhances the proliferation of GAT-specific T cells; (ii) the anti-idiotypic serum is effective in priming in vivo LNC which then acquire the capacity to proliferate specifically with GAT in vitro. These results further confirm the existence of idiotype-like determinants on T cells.

Animals↗
PubMed1982

Uridine as the only alternative to pyrimidine de novo synthesis in rat T lymphocytes.

Concanavalin A-induced proliferation of rat T-lymphocytes is completely inhibited by 10(-5) M pyrazofurin, a potent inhibitor of pyrimidine de novo synthesis, as judged by cell viability and [3H]thymidine incorporation. Proliferation is completely restored by 5 X 10(-5) M uridine. Cytidine, deoxycytidine, deoxyuridine and thymidine 10 X 10(-5) M each, fail to re-establish proliferation but produce an isotropic dilution of [3H]thymidine uptake in DNA. Bases (cytosine, uracil and thymine) neither restore proliferation nor induce isotopic dilution. The unexpected inability of cytidine to reverse de novo pyrimidine synthesis inhibition suggests a lack of cytidine deaminase activity in rat T-lymphocytes. This is confirmed by a direct sensitive radioisotopic assay (less than 0.001 nmol X min-1 X 10(-6) cells).

Amides↗
PubMedDate not supplied

Public idiotopes and/or internal images in the anti-poly(Glu60Ala30Tyr10) response: analysis by monoclonal antibodies.

From BALB/c mice immunized with BALB/c polyclonal anti-GAT antibodies, we have obtained monoclonal antiidiotypic antibodies directed against public idiotopes expressed following GAT (Glu60Ala30Tyr10) immunization in all individuals of all mouse strains tested. Nine monoclonal anti-Id antibodies were studied in detail. One of these monoclonals recognizes only polyclonal anti-GAT antibodies; the other eight recognize polyclonal anti-GAT antibodies and monoclonal anti-GAT antibodies. The distribution of the structures recognized by the different monoclonal anti-Id on a battery of twenty monoclonal anti-GAT antibodies allows a definition of two families of public idiotopes. The significance of the existence of these two families is discussed in light of the hypothesis recently proposed by Jerne et al. (EMBO J., 1982, 1, 243-247) who consider that the induction of internal images of antigen during immunization leading to the production of antiidiotypic reagents is responsible for the existence of public idiotopes. Our present results may be interpreted to indicate that even though certain monoclonal anti-Id reagents could be internal images of the antigen, the others do, in fact, recognize public idiotopes. Therefore, the notion of internal image does not exclude the existence of public idiotypic specificities.

Animals↗