Comparative studies on the roles of mediator molecules in expression of the suppressor activity of Mycobacterium avium complex-induced immunosuppressive macrophages against T cell and B cell mitogenic responses

Abstract

Summary Mycobacterium avium complex-induced immunosuppressive macrophages (MAC-MΦs) exhibit suppressor activity against concanavalin A-induced T cell mitogenesis (T cell Con A mitogenesis). We examined the profiles of the MAC-MΦ-mediated suppression of lipopolysaccharide-induced B cell mitogenesis (B cell LPS mitogenesis) and found the following. First, although NG-monomethyl-L-arginine and carboxy-PTIO effectively blocked the MAC-MΦ’s suppressor activity against T cell Con A mitogenesis, MAC-MΦ’s action against B cell LPS mitogenesis was only weakly affected by these NO-reducing agents. Second, B cell LPS mitogenesis was remarkably more susceptible to MAC-MΦ-derived reactive oxygen intermediates than T cell Con A mitogenesis. Third, B cell LPS mitogenesis was less susceptible to the inhibitory effects of the other MAC-MΦ-derived suppressor mediators, including free fatty acids, TGF-β and prostaglandin E2, than T cell Con A mitogenesis. Fourth, MAC-MΦ’s suppressor activity was strongly dependent on B7-1 like molecule-mediated cell contact with target cells only in the case of T cell Con A mitogenesis. Therefore, there are significant differences in the modes of suppressor action of MAC-MΦs against T cell and B cell mitogenesis.