Rapid early onset lymphocyte cell death in mice resistant, but not susceptible to Leishmania major infection

Leishmania major (Lm) infection in mice is a prototypical model for the rol e of immune deviation in disease resistance. Resistant strains of mice deve lop a Th1 response to Lm infection, distinguished by secretion of IL-12 and interferon gamma. In contrast, susceptible strains display sustained IL-4 expression characteristic of a Th2 response. However, when mechanisms of ce ll death are blocked, mice display a susceptible phenotype even in the pres ence of a strong Th1 response, suggesting that cell death, and not cytokine bias, may be an importnt factor in disease resistance. Here, we investigat ed this hypothesis by comparing lymphocyte cellularity, cell death and Fas expression in resistant CBA and susceptible BALB/c mice during the course o f Lm infection. We found that delayed onset of cell death and late Fas indu ction correlated with massive lymphocyte accumulation and susceptibility to leishmaniasis, while early cell death and rapid Fas induction occurred in resistant mice.