Monocyte chemoattractant protein-1-dependent increase of V alpha 14 NKT cells in lungs and their roles in Th1 response and host defense in cryptococcal infection

To elucidate the role of NKT cells in the host defense to cryptococcal infe ction, we examined the proportion of these cells, identified by the express ion of CD3 and NK1.1, in lungs after intratracheal infection with Cryptococ cus neoformans. This population increased on day 3 after infection, reached a peak level on days 6-7, and decreased thereafter. In V alpha 14 NKT cell -deficient mice, such increase was significantly attenuated. The proportion of Va14 NKT cells, detected by binding to alpha -galactosylceramide-loaded CD1d tetramer, and the expression of V alpha 14 mRNA increased after infec tion with a similar kinetics. The delayed-type hypersensitivity response an d differentiation of the fungus-specific Th1 cells was reduced in V alpha 1 4 NKT cell-deficient mice, compared with control mice. Additionally, elimin ation of this fungal pathogen from lungs was significantly delayed in V alp ha 14 NKT cell-deficient mice. Production of monocyte chemoattractant prote in (MCP)-1 in lungs, detected at both mRNA and protein levels, increased on day 1, reached a peak level on day 3, and decreased thereafter, which prec eded the increase in NKT cells. Finally, the increase of total and V alpha 14(+) subset of NKT cells after infection was significantly reduced in MCP- 1-deficient mice. Oar results demonstrated that NKT cells, especially V alp ha 14(+) subset, accumulated in a MCP-1-dependent manner in the lungs after infection with C. neoformans and played an important role in the developme nt of Th1 response and host resistance to this fungal pathogen.