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

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Abstract
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.

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