Apoptotic deletion of Th cells specific for the 19-kDa carboxyl-terminal fragment of merozoite surface protein 1 during malaria infection

Immunity induced by the 19-kDa fragment of merozoite surface protein 1 is d ependent on CD4(+) Th cells. However, we found that adoptively transferred CFSE-labeled Th cells specific for an epitope on Plasmodium yoelii 19-kDa f ragment of merozoite surface protein 1 (peptide (p)24), but not OVA-specifi c T cells, were deleted as a result of P. yoelii infection. As a result of infection, spleen cells recovered from infected p24-specific T cell-transfu sed mice demonstrated reduced response to specific Ag. A higher percentage of CFSE-labeled p24-specific T cells stained positive with annexin and anti -active caspase-3 in infected compared with uninfected mice, suggesting tha t apoptosis contributed to deletion of p24-specific T cells during infectio n. Apoptosis correlated with increased percentages of p24-specific T cells that stained positive for Fas from infected mice, suggesting that P. yoelii -induced apoptosis is, at least in part, mediated by Fas. However, bystande r cells of other specificities also showed increased Fas expression during infection, suggesting that Fas expression alone is not sufficient for apopt osis. These data have implications for the development of immunity in the f ace of endemic parasite exposure.