Characteristics of immunosuppressive macrophages induced in spleen cells by Mycobacterium avium complex infections in mice

Abstract
SUMMARY: The profile of generation and characteristics of splenic macrophages (MØs) which suppress the concanavalin A (Con A) mitogenic response of splenic T cells (designated as ‘immunosuppressive MØ’) in host CBA/JN mice during the course of Mycobacterium avium complex (MAC) infection were investigated. In MAC-infected mice, reductions in some cellular functions of host splenic T cells, such as the Con A mitogenic response and mixed leucocyte reaction, were seen around 2 weeks after challenge of organisms, and this was accompanied by appearance of immunosuppressive MØs in spleen cells. In this case, increase in immunosuppressive MØ activity was seen in terms of both activity per spleen and activity per individual MØ. In this phase of the infection, MAC-induced splenic MØs showed a markedly increased ability to produce reactive oxygen radicals in response to phorbol myristate acetate. Thus, the expression of suppressor activity of MAC-induced MØs seems to be closely linked to their activated state. A large proportion of the immunosuppressive MØs exhibited suppressor activity dependent on prostaglandins and membrane functions related to microfilaments. It was also found that the generation of IL-2-reactive T cell populations in response to Con A was markedly inhibited by MAC-induced splenic MØs, whereas they caused no significant reduction in the IL-2-producing ability of normal spleen cells.