Histamine-induced suppressor factor (HSF): inhibition of helper T cell generation and function

The effect of histamine-induced suppressor factor (HSF) on the humoral immune response was examined with the model of polyclonal B cell activation induced during a primary mixed lymphocyte culture (MLC). The number of plaque-forming cells (PFC) generated during MLC was measured by a protein A plaque assay. HSF was produced by incubating lymphocytes from normal subjects with 10(-4) M histamine. The addition of HSF on day 0 to MLC-induced plaques reduced the mean number of IgG, IgM, and IgA PFC by 60 to 80%. HSF supernatants were active at a titer of 1/1000 and suppressed IgG, IgM, and IgA isotypes equally. To study the effect of HSF on the T helper cell component of this reaction, purified T lymphocytes were activated in undirectional MLC and subsequently combined with unprimed B cells to induce a polyclonal PFC response. HSF present during the generation phase of activated T cells or only at the time of co-culture inhibited the total PFC response by 83 +/- 13% and 76 +/- 23%, respectively. The expression of "Ia" and autologous DR antigens normally detected on 50 to 62% of activated T cells generated during MLC were reproducibly reduced to 20% in the presence of HSF. Similarly, the polyclonal B cell response inducible by MLC-derived helper factors (1500 IgG PFC/10(6)) was markedly inhibited. Thus, HSF inhibits MLC-induced polyclonal B cell activation by interfering with the generation and effector function of T helper cells as well as the B cell response to preformed helper factors.