Modulation of lymphocyte activation by soluble Brugia pahangi extracts

Both nonspecific and antigen specific immunological alterations are associated with the presence of circulating microfilariae in Brugia pahangi infected jirds. T-cell growth factors are an essential element of an immune response; thus, modulation of the production or utilization of lymphokines by filarial antigens may be involved in these alterations. In the present study, the effect of soluble extracts of B. pahangi adult worms and microfilariae on the in vitro mitogen and antigen induced proliferative responsiveness of lymphocytes from uninfected and B. pahangi immunized jirds was investigated. Dose dependent suppression of lymphocyte proliferative responsiveness to the T-cell mitogen, concanavalin A ranged from 37% to 86% in the presence of adult or microfilarial (Mf) extracts, respectively. Similarly, a suppressive effect was observed when other mitogens were used to stimulate the lymphocytes. Mf extracts did not significantly suppress the proliferative response of lymph node cells from B. pahangi immunized jirds to parasite antigen. However, microfilarial fractions higher than 150 Kd, purified by gel filtration HPLC, consistently suppressed antigen as well as mitogen responses. Soluble extracts of B. pahangi females and Mf also suppressed mitogen induced lymphokine production by lymph node cells by 66% and 68% respectively. These findings suggest that a microfilarial-derived antigen may play a role in regulating immune reactivity in filarial infections. The absence of generalized nonspecific immunosuppression in filarial infections, however, suggests that the effect of microfilarial-derived antigens may be restricted to the microhabitat of the parasite.