Effects of mitogens and lymphokines on the regulation of the immune response to HBs antigen in vitro.

We studied the immunoregulatory mechanisms of responsiveness and non-responsiveness to hepatitis B (HB) vaccine by analysing the influence of HB surface antigen (HBsAg) on lymphokine- or mitogen-stimulated peripheral lymphocytes from healthy volunteers. Stimulation with pokeweed mitogen (PWM) led to a reduced production of polyclonal IgG from responder cells compared to non-responder lymphocytes. PWM did not enhance the HBs-specific IgG production from responder lymphocytes when the cells were obtained at Day 10 after the last vaccination. A slight reduction of the proliferative response was observed when lymphocytes of non-responders were stimulated with phytohaemagglutinin (PHA) or concanavalin A (Con A). Production of HBs-specific antibodies was enhanced by incubating responder lymphocytes with interleukin-4 (IL-4). The HBs antigen itself did not modulate the expression of the CD23 B-cell differentiation antigen in unseparated lymphocytes. However, CD23 expression induced by low doses of IL-4 was markedly enhanced in an antigen-specific way. Our data indicate that HBs antigen enhances the lymphokine-induced CD23 expression, whereas the mitogen-induced CD23 expression is not affected. Lymphocytes obtained from non-responders exerted a reduced expression of CD25 surface antigen compared to responder lymphocytes. Exogeneous addition of IL-2 in the absence or presence of HBsAg induced a marked enhancement of the IL-2 receptor expression in responder lymphocytes. Furthermore, no significant modulation of CD25 expression was observed in non-responder lymphocytes.