The specific aims of this proposal are: (1) to determine whether two strains of C. neoformans which differ in virulence also differ in their ability to induce TNFalpha production in the lungs and to determine whether TNFalpha expression is T cell dependent (2) to define the role of TNFalpha in mediating the pulmonary clearance of C. neoformans, the recruitment of subpopulations of leukocytes into the lungs, and the development of C. neoformans specific T cells (3) to examine the effect of melanin production by C. neoformans on pulmonary inflammation, cryptococcal clearance and expression of TNFalpha, and (4) to determine whether protective T cell immunity to a virulent strain of C. neoformans can be induced by increasing the levels of TNFalpha in the lungs. The latter experiments may define if adjunct therapy with TNFalpha is feasible in the treatment of this infection.
