Marie Sarfati

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.

Characterization of Cellular Infiltrates in Skin Lesions of Atopic Eczema by Means of Monoclonal Antibodies

Frozen skin biopsies from 3 acute and 3 chronic lesions of atopic dermatitis were examined by means of various ortho-monoclonal antibodies (OKT3, 4] not equal to----4, OKT6, OKT8; OKIa and OKM1) in an indirect immunofluorescence technique. The results show that both T helper (T4) and T suppressor cytotoxic (T8) lymphocytes are present in the inflammatory infiltration which predominantly contained Ia mononuclear cells. Despite the absence of double staining procedure, the observations suggest that T4 cells predominate over T8 cells in the acute lesions whereas the reverse tendency is noted in the chronic lesions. T8 cells are found mainly in the superficial dermis or even in the epidermis; by contrast, T4 cells tend to be more deeply located in the dermis. The lesions are characterized by a dramatic increase in the number of Langerhans cells (OKT6, OKIa+) that are found not only in the epidermis but also in the dermis.

Induction of IgA-specific suppressor activity in human T-lymphocyte cultures

Cell-free supernatants of human circulating T-lymphocyte cultures incubated with secretory IgA (S-IgA) specifically suppressed both spontaneous IgA synthesis by B lymphocytes isolated from allergic individuals and pokeweek mitogen-induced IgA secretion by peripheral blood mononuclear cells. Cell-free supernatants of T-cell cultures incubated with IgE had no effect on IgA, IgG, or IgM synthesis. Hence, it is concluded that upon incubation with S-IgA, but not with another Ig class, T lymphocytes release IgA-specific suppressor factors.

Demonstration of intracytoplasmic IgE in circulating lymphocytes of allergic individuals

Cells containing intracytoplasmic IgE (IC IgE) were demonstrated in the peripheral blood mononuclear cells of atopic individuals by means of indirect immunofluorescence, employing mouse monoclonal anti-human IgE antibody. IC IgE-positive cells are low-density B cells as shown by centrifugation on discontinuous bovine serum albumin density gradient and by their reactivity with B1 monoclonal antibody specific to B lymphocytes, respectively. Further characterization of these cells by means of a rosette assay employing anti-Ig-coupled bovine erythrocytes indicated that these cells were surface IgE (sIgE) positive and sIgM negative. The data strongly suggest that activated IgE B cells are circulating in the blood of allergic individuals.