Characterization of a suppressor factor that regulates phagocytosis by macrophages in murine cryptococcosis

Abstract

A T-suppressor factor which inhibits the phagocytic activity of a macrophage subset has been further characterized. This suppressor factor was first described for a murine model of cryptococcosis but was later found to be common to models of immunologic unresponsiveness. The suppressor factor was produced when suppressor cells were cultured in the presence of specific cryptococcal antigen. It could not be extracted from spleen cells and was not induced by antigen in cultures of lymph node cells. The suppressor factor was filtered through Amicon filters of 100-kilodalton (kDa) exclusion limit but was retained by filters excluding molecules of less than 50 kDa. By Sephadex G-100 chromatography, the factor eluted just ahead of bovine serum albumin (68 kDa). The activity of the suppressor factor could not be inhibited by anticryptococcal antibody, but it was inhibited by anti-I-J alloantiserum of the same genotype as the lymphocyte which produced the factor. Absorption with an encapsulated strain of Cryptococcus neoformans removed the suppressor factor from culture supernatants, while absorption with a nonencapsulated mutant or an unrelated yeast cell had not effect. On the basis of these observations, it was apparent that the suppressor factor was idiotypic in nature and that I-J and/or the I-J-interactive molecule played a role in the function of the suppressor factor. The requirement for antigenic stimulation for the production of suppressor factor in vitro distinguished it from the T-suppressor factor 3 described by others which regulates delayed-type hypersensitivity in cryptococcosis.