B cells shape T cell responses during Pneumocystis infection (P3053)

Abstract

Abstract Pneumocystis pneumonia (PCP) remains one of the leading causes of death in immunocompromised patients. Disease is attributed to the loss of CD4 T cells; however recent studies suggest that B cells also play a protective role in clearing PC in an Ig-independent manner through antigen presentation. Several patients treated with anti-CD20 have developed PCP and thus we investigated the effect of anti-CD20 on primary PC infection. We hypothesized that B cells in part function as a critical antigen-presenting cell to helper T cells. To test this, C57BL/6 WT mice were administered anti-CD20, anti-CD4 (as a pos. control) or both, and then infected with a 105 inoculum of Pneumocystis murina. Lung mononuclear cells were harvested two weeks after infection, assessed for cellularity and then stimulated in vitro with PC antigen for cytokine profiling. Even though CD20-depleted animals had unaltered T cells numbers, there were diminished cytokine responses for IL-5, IL-17, and IL-10. These data suggest that B cells are involved in mediating optimal T cell cytokine responses against PC. We are currently testing if B cells are required in the recall responses from memory T cells by performing B cell depletion during the re-challenge of mice that have recovered from primary PC infection. We are also investigating if B cells modify T regulatory cells during Immune Reconstitution Inflammatory Syndrome (IRIS), a disease that affects a subset of patients upon reconstitution of CD4+ cells.