Interleukin-4 suppresses immunoglobulin production by peripheral blood lymphocytes of patients with common variable immunodeficiency (CVI) induced by supernatants of T cell clones

Abstract

Supernatants of both CD4+ and CD8+ alloreactive T cell clones induced IgM, IgG and IgA synthesis by peripheral blood lymphocytes (PBL) of healthy donors in vitro. These supernatants were also tested on their capacity to induce immunoglobulin production by PBL of four patients with CVI and one patient with CVI and thymoma. A low degree of IgM, IgG and IgA production was induced in one patient with CVI. In the patient with CVI and thymoma, induction of IgG and IgA synthesis was in the normal range, whereas IgM production was reduced. In the three other patients only a low production of IgM was induced. Interestingly, pre-incubation of the PBL for 24 h with interleukin-4 (IL-4) suppressed immunoglobulin production both by PBL of the patients with CVI and healthy donors. The strongest inhibitory effects were observed on IgA synthesis. These data indicate that B cells of three patients with CVI can not be induced to switch to IgG or IgA producing cells in vitro. In contrast, B cells of the patient with CVI and thymoma were able to respond to the relevant B cell growth and differentiation factors present in the T cell clone supernatants, suggesting that the T cells of this patient may fail to produce these factors. However, the proliferative responses of the T cells to phytohaemagglutinin (PHA), concanavalin A (Con A) and pokeweed mitogen (PWM), were normal in all five patients tested. In addition, the interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) production by PBL of the five patients was also in the normal range. Although only a small number of patients was tested, these results support the view that defects in both regulatory T cell functions and/or intrinsic B cell defects may contribute to the pathogenesis of CVI.