This laboratory has been investigating a specific, anti-cryptococcal CD4+ T cell-mediated acquired resistance mechanism that allows the vaccinated immunocompetent mouse that has been re-challenged with an ordinarily lethal systemic C. neoformans infection to eradicate yeast that has already gained access to the brain. Even after activation, further interaction between CD4+ cells and class II MHC-bearing cells in the brain (i.e., recruited macrophages or resident glial cells) is required for effective yeast-killing to occur.
The aim of this study is to further elucidate this protective mechanism, and to look for ways to circumvent the requirement for CD4+ T cells, as such information may be useful in designing immunotherapies to augment conventional chemotherapy for cryptococcal meningoencephalitis in AIDS patients and other immunodeficient individuals. The goals of the study are: 1. To investigate the hypothesis that CD4+ T cells work in the brain by activating macrophages or glial cells to kill yeast; 2. To determine if CD4+ T cells must be the source of protective cytokines; 3. To determine whether CD8+ T cells can substitute for anti-cryptococcal CD4+ T cells in immunocompromised mice and 4. To investigate the fungicidal mechanism employed by effector cells in the brain. This will be accomplished by comparative experimental infection of immunocompetent mice and assaying cytokine mRNA and protein by RT-PCR and intracellular cytokine staining of lymphocytes harvested from the site of infection.
