Functional T cells in primary immune response to histoplasmosis

Functional T cells are critical to host defense against infection. It has been reported that functional T cells as determined by their cytokine production represent antigen-specific T cells in infectious disease models. In this study, we enumerated Histoplasma-specific interferon gamma-producing cells in bulk splenocyte culture and showed that infection with Histoplasma capsulatum, an intracellular pathogen of the macrophage, activated both CD4 and CD8 T cells. The magnitude of CD8 T cell response was lower than CD4 T cell, but the expansion and contraction of both cell types followed the same kinetics. Over 90% of interferon gamma-producing CD4 T cells and >85% of CD8 T cells expressed CD44(hi) phenotype. The strong correlation between interferon gamma production and CD44(hi) expression was observed not only at the peak of response but also throughout the course of infection. Moreover, a broad spectrum of Vbeta populations responded to systemic as well as pulmonary infections, suggesting no obvious T cell receptor bias in primary immune response to histoplasmosis. While each Vbeta population contributed to interferon gamma production, several specific Vbeta populations made up higher percentages of interferon gamma-producing cells. Our study laid the groundwork for further investigations in immune response to histoplasmosis.