The capsule of Cryptococcus neoformans reduces T-lymphocyte proliferation by reducing phagocytosis, which can be restored with anticapsular antibody

Cell-mediated immunity is critical for the host defense to Cryptococus neof ormans, as demonstrated by numerous animal studies and the prevalence of th e infection in AIDS patients, Previous studies have established that the po lysaccharide capsule contributes to the virulence of C, neoformans by suppr essing T-lymphocyte proliferation, which reflects the clonal expansion of T lymphocytes that is a hallmark of cell-mediated Immunity. The present stud ies were performed to identify the major mechanism by which polysaccharide impairs lymphocyte proliferation, since capsular polysaccharide has the pot ential to affect the development of T-lymphocyte responses by stimulating p roduction of interleukin-10 (IL-10), inhibiting phagocytosis, and inducing shedding of cell surface receptors, We demonstrate that polysaccharide inhi bits lymphocyte proliferation predominantly by blocking uptake of C. neofor mans, which is crucial for subsequent lymphocyte proliferation. In addition , we show that polysaccharide did not suppress lymphocyte proliferation via an IL-10-dependent mechanism, nor did it affect critical surface receptor interactions on the T cell or antigen-presenting cell. Having established t hat polysaccharide impairs phagocytosis, we performed studies to determine whether opsonization with human serum or with anticapsular antibody could r everse this effect. Impaired uptake and lymphocyte proliferation that were induced by polysaccharide can be enhanced through opsonization with monoclo nal antibodies or human serum, suggesting that antipolysaccharide antibodie s might enhance the host defense by restoring uptake of the organism and su bsequent presentation to T lymphocytes, These studies support the therapeut ic potential of stimulating cell-mediated immunity to C, neoformans,vith an ticapsular antibody.