The cell wall and membrane of Cryptococcus neoformans possess a mitogen for human T lymphocytes

The mechanism of human T-lymphocyte activation by the pathogenic yeast Cryp tococcus neoformans has not been established. Previous investigations have suggested that C. neoformans contains a mitogen for T lymphocytes, while ot her investigators have attributed lymphocyte proliferation in vitro to a re call antigen. Because of the potential importance of the mechanism of T-cel l activation for our understanding of the immune response to C. neoformans, the present studies were performed to determine whether C. neoformans cont ains a mitogen for T lymphocytes. C. neoformans stimulates fetal blood lymp hocytes to proliferate and stimulates proliferation of CD45RA(+) cells from adults, indicating that it stimulates naive T cells. The T-cell response t o C. neoformans was dependent upon the presence of accessory cells. However , allogeneic cells were sufficient for accessory cell function, indicating that the response was not major histocompatibility complex restricted. The percentage of T cells in the cell cycle was higher than that with the recal l antigen tetanus toroid but lower than that with the mitogenic lectin phyt ohemagglutinin A or the superantigen Staphylococcus enterotoxin B. Precurso r frequency analysis established that 1 in 7,750 +/- 2,270 T cells prolifer ated in response to the cryptococcal cell wall and membrane. Compared to th e case for most mitogens or superantigens, the proliferative response is la te and the number of T cells that enter the cell cycle and the precursor fr equency are low, indicating that the mitogenic effect is modest. However, t he mitogenic effect of C. neoformans should be considered when interpreting the immune response to C. neoformans, since even weak mitogens can have pr ofound effects on host defense.