The host response of CD28-deficient mice to Pneumocystis infection.

Pneumocystis infection leads to a life threatening pneumonia in susceptible individuals. While depletion or dysfunction of CD4+T cells is a key determinant of susceptibility to Pneumocystis, the host response that leads to resolution of infection or lung injury is less well understood. We had previously shown that mice deficient in the T cell costimulatory molecule CD28 are susceptible to infection with Pneumocystis. A detailed analysis revealed that they clear Pneumocystis with delayed kinetics. This is associated with an influx of naïve CD8+ T cells. Depletion of CD8+ T cells did not alter organism burden, suggesting these cells are not responsible for clearance. Analysis of the cytokine milieu demonstrated a consistent increase in mRNA for IL-10 and IFN-gamma in the CD28-deficient mice. These data suggest that CD28 function in important in the efficiency of the host response to Pneumocystis pneumonia.