Studies on the nature of antigen specific immune regulation during Brugia pahangi infection in the jird, Meriones unguiculatus
Description
Immunoregulatory mechanisms may contribute in as yet undefined ways to the persistence of chronic filarial infections. In previous studies of jirds infected with Brugia pahangi, the onset of microfilaremia was correlated with both parasite-specific and nonspecific regulatory alterations. The present investigations were designed to extend these observations by characterizing the suppressor cells induced by B. pahangi infection and to describe the relationship between specific and nonspecific regulatory phenomena. Cells capable of suppressing in vitro proliferative responses to B. pahangi antigens appeared in the spleen 10-12 weeks post-infection, were plastic nonadherent, resistant to cyclophosphamide, and bore receptors for histamine, peanut agglutinin, soybean agglutinin, and jird immunoglobulin (Fc). In contrast, cells capable of regulating the mitogen responsiveness of normal cells first appeared in the spleen approximately 20 weeks post-infection, were adherent to plastic, and were sensitive to cyclophosphamide. Experiments examining the effect of irradiated, antigen-stimulated cells on the mitogen responsiveness of normal cells demonstrated that regulatory activity was not observed prior to 20 weeks post-infection and was predominantly restricted to the spleen. Furthermore, the dependence of antigen-induced suppression of mitogen responsiveness on histamine adherent, plastic adherent, and cyclophosphamide sensitive cells suggests that antigen specific and nonspecific suppressor cells comprise a single regulatory circuit. Investigation of the effect of jird serum on in vitro antigen and mitogen induced proliferation suggests that serum factors may contribute to regulation of parasite specific responses. Sera (1%) from chronically infected jirds, but not acutely infected or microfilaremic jirds suppresses antigen responsiveness. Inhibitory effects were associated with high molecular weight (> 100,000) factors which were not bound by protein A, anti-jird IgG, or B. pahangi antigen and which were not precipitated by polyethylene glycol