Presentation of cryptococcal capsular polysaccharide (GXM) on activated antigen-presenting cells inhibits the T-suppressor response and enhances delayed-type hypersensitivity and survival

A hallmark of infection with Cryptococcus neoformans is depression of the immune system characterized by poor inflammatory responses and loss of delayed-type hypersensitivity (DTH) and antibody responses. T-suppressor cell (Ts) responses, elicited by the capsular polysaccharide (GXM) of the organism, are known to develop during infection. This study was undertaken to develop a method to inhibit the anti-GXM Ts response and thereby study the influence of the Ts response on immune responsiveness and survival in cryptococcosis. Antigen-presenting cells (APC), elicited with complete Freund's adjuvant (CFA), were treated in vitro with GXM (GXM-APC). The GXM-APC were injected intravenously into normal mice. These mice were resistant to induction of anti-GXM Ts cells when soluble GXM was administered in tolerogenic doses or when animals were infected with C. neoformans. Inhibition of the anti-GXM Ts response was specific to GXM as levan-APC did not inhibit induction of anti-GXM Ts cells. Inhibition of the anti-GXM Ts response could not be attributed to increased clearance of GXM due to induction of anti-GXM antibodies or other mechanisms. Anti-cryptococcal DTH responses were lost in mice by the second week of infection. However, treatment with GXM-APC, but not levan-APC, allowed mice to maintain their DTH response. GXM-APC pretreatment enhanced survival of infected mice compared with mice pretreated with levan-APC. These results show that GXM-APC induces immune responses that inhibit the induction of Ts responses and enhances DTH responses in infected mice. These responses correlate with enhanced survival after cryptococcal infection.