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Biomedical subjects

G Delespesse

Publications and source records attributed to G Delespesse.

At least 37 records · Page 2Linked to original sources

Antiproliferative effect of interleukin-4 in B chronic lymphocytic leukemia.

Recombinant interleukin-4 (IL-4) profoundly inhibits the proliferative response of chronic lymphocytic leukemic B cells (B-CLLs) to recombinant interleukin-2 (IL-2). In the present study, we confirmed and extended these data by showing that IL-4 strongly suppresses the [3H]thymidine incorporation by B-CLLs stimulated by recombinant tumor necrosis factor alpha, recombinant interferon alpha, IL-2, and low molecular weight B cell growth factor in the absence of costimulant. Recombinant interleukin-4 inhibits spontaneous DNA synthesis suggesting that it also interferes with the autocrine proliferation of these cells. Kinetic studies indicate that IL-4 suppresses rather than shifts the peak of cytokine-induced DNA synthesis. Moreover, IL-4 blocks the progression of B-CLLs in or into G1 stage of the cell cycle as shown by the inhibition of cytokine-induced [3H]uridine incorporation. Finally, IL-4 pretreatment of B-CLLs prevents their subsequent proliferative response to the above cytokines, indicating that IL-4 confers to the B-CLLs a state of resistance to numerous stimulatory cytokines. The antiproliferative effects of IL-4 suggest that this lymphokine may have important therapeutic implications for the B-CLL patients.

Cell Cycle

Gamma-interferon promotes the release of IgE-binding factors (soluble CD23) by human epidermal Langerhans cells.

In a previous study, we have demonstrated that human epidermal Langerhans cells (LC) are induced to express Fc epsilon R2/CD23 by stimulation with IL-4 and/or IFN-gamma. In this study, using LC-enriched and LC-depleted epidermal cell (EC) cultures, we have shown that stimulation with IL-4 and/or IFN-gamma not only led to Fc epsilon R2/CD23 expression on normal human LC but also to the release of significant amounts of IgE-BF (soluble CD23). Furthermore, stimulation with IL-4 was more effective in induction of Fc epsilon R2/CD23 on LC when compared to IFN-gamma, which, in contrast, strongly promoted the release of IgE-BF. These results indicate that Fc epsilon R2/CD23-positive LC represent a potential source of IgE-BF and that, as is observed in monocytes or U937 cells, IFN-gamma and IL-4 differently regulate the Fc epsilon R2/CD23 expression and release on LC.

Antigens, Differentiation, B-Lymphocyte

New concepts of IgE regulation.

B cell switch to IgE expression is mediated by IL-4 and is regarded as a T helper cell-related phenomenon. In this overview we describe that IgE switch can also be induced by mast cell/basophil like cells (from splenic non-B, non-T cells), activated by IgE receptor cross-linking and/or IL-3 which results in IL-4 production by these cells. Furthermore, activated mast cells produce their own growth factors, IL-3 and GM-CSF. Thus, activation of mast cells can provoke an ongoing local allergic reaction as long as antigen confrontation is maintained, a process which is sustained by further IgE production as well as renewal of mast cells. It is furthermore demonstrated that in certain established immune situations the IgE response may become independent of IL-4, namely in the spontaneous in vitro IgE expression of cells from atopic individuals as well as in an in vitro antigen-induced secondary IgE response of spleen cells derived from previously immunized mice. Thus, IgE-switched B cells may persist in vivo and may represent a pool of potentially IgE-producing cells. Finally, a selective inhibition of the IgE response is described in vitro and in vivo by the use of so-called non-anaphylactic monoclonal anti-IgE antibodies. Such antibodies bind to surface IgE+ B cells, but not to IgE-sensitized mast cells, and thereby inhibit IgE responses. Non-anaphylactic antibodies blocked the binding of allergen-specific IgE to mast cells by competing with the Fc epsilon on these cells. As a consequence they do not induce but rather prevent allergen-induced mediator release by mast cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Glucocorticoids increase the synthesis of immunoglobulin E by interleukin 4-stimulated human lymphocytes.

This study indicates that hydrocortisone (HC) markedly increases the synthesis of immunoglobulin E (IgE) by interleukin 4 (IL-4)-stimulated human lymphocytes. The effect is glucocorticoid specific and is obtained with low concentrations of HC (0.1-10 microM). In both the early and the late phase of the IL-4-induced response HC exerts its effects which are respectively IL-4 dependent and IL-4 independent. The IgE potentiation cannot be explained by the inhibition of interferon-gamma (IFN-gamma) production since it is observed in the absence of endogenous secretion of IFN-gamma. HC inhibits the production of IgE-binding factors (soluble CD23) and the expression of the low-affinity receptor for IgE, also known as the (Fc epsilon RII) CD23 antigen; however, the residual expression of Fc epsilon RII by IL-4- and HC-treated peripheral blood mononuclear cells (PBMCs) is important since the IgE response of these cells is markedly inhibited by anti-CD23 monoclonal antibody. HC acts mainly by amplifying the cellular interactions between monocytes and lymphocytes; indeed, HC has no effect on monocyte-depleted PBMCs, and moreover, monocytes cannot be replaced by soluble factors. Most importantly, T cells are not required for the induction of IgE synthesis by costimulation with IL-4 and HC. However, the IgE response of rigorously T cell-depleted PBMCs may be further increased by the addition of T cells. Further analysis of the permissive effect of HC on the synthesis of IgE by T cell-depleted PBMCs suggests that HC acts in synergy with IL-4 to trigger the activation and the differentiation of B cells into IgE-producing cells.

Antigens, CD

Distribution of beta-adrenergic receptors on human lymphocyte subpopulations.

A technique is described allowing the quantification and the characterization of specific beta-adrenergic receptors in intact living human lymphocytes. 125I-Iodohydroxybenzylpindolol, a potent beta-adrenergic antagonist was used to label specific binding sites on unfractionated lymphoid cells and on purified subpopulations of T (F1 and F2) and B cells. F1 and F2 were obtained by filtration through nylon wool column as previously described (Delespesse et al., 1976), they differ in their response to mitogens, and in their interactions with adherent cells and B cells. 125I-HYP binding to unfractionated lymphocytes was a saturable, stereospecific and rapid process with a dissociation constant of 2.5 10(-10) M and a binding capacity of 400--600 sites/cell. Bindings on unfractionated lymphocytes, purified B cells and T cells of the F2 fraction were similar. No detectable binding was noted on T cells from the F1 fraction. Enriched T cells obtained by a rosetting technique displayed 200 receptors/cell.

Adrenergic beta-Agonists

Circulating immune complexes in various thyroid diseases.

In a study of 171 patients with various thyroid diseases, circulating immune complexes (CIC), measured by a C1q solid phase radioassay, were detected in 26% of the patients as compared to 8% of the control subjects. CIC were found in 33--55% of the patients with a well defined thyroid autoimmune disorder (Hashimoto's goitre, asymptomatic thyroiditis, spontaneous myxoedema and Graves' disease) and also in the same proportion of patients with diffuse goitre. CIC were correlated to the presence of serum antibodies to microsomal thyroid antigen but not to their titre. No relationship was observed between CIC and the age or sex of the patients and the presence of exophthalmos, or between CIC and the different thyroid function tests or serum anti-thyroglobulin antibodies. CIC were found in untreated patients as well as in those treated with prednisone, methimazole or thyroxine.

Adolescent

[Incidence of antispermatozoidal antibodies in the serum of fertile women (author's transl)].

The authors describe a simple and reproducible-microagglutination technique for the detection of antispermatozoa antibodies. A positive reaction is detected in 2 p. 100 of women with a normal fertility (12/516), in 10 p. 100 of pregnant women (4/40) and in 32.5 p. 100 of patients with recurrent abortions. There is no relation between anti-HLA antibodies and the sperm agglutinating activity of a serum.

Abortion, Habitual

Influence of ageing on IgE-mediated reactions in allergic patients.

The influence of age and sex has been evaluated in 326 allergic patients on the following parameters: total serum IgE concentration, serum concentration of specific IgE antibodies against seventeen common allergens, mean number of positive allergens, absolute numbers of circulating eosinophils, corticosteroid dependence and response to sodium cromoglycate (DSCG). The results indicate that age and sex significantly influence the IgE antibody production in these patients. The data strongly suggests the appearance during ageing of a progressive natural desensitization. This contrasts with the increased frequency of corticosteroid-dependent cases during ageing. There is an inverse relation between age and response to DSCG therapy.

Adolescent

Methylmethacrylate hypersensitivity in orthopaedic surgery.

The sensitivity to methylmethacrylate monomer in 25 patients undergoing orthopaedic surgery was studied. No relation could be found between the cardiovascular reactions observed during the cementation of the femoral prosthesis and the complement system, investigated by measuring the serum concentration of the haemolytic complement, components 3 and 4.

Aged