Blood stage malaria antigens induce different activation-induced cell death programs in splenic CD4⁺ T cells

Abstract

CD4⁺ T cells respond to antigen immunization through a process of activation, clonal expansion to generate activated effector T cells followed by activation-induced clonal deletion of the responding T cells. While loss of responding T cells in post-activation death by apoptosis is a major factor regulating immune homeostasis, the precise pathways involved in downsizing of Plasmodium falciparum antigen-induced T cell expansions are not well characterized. We report in this study that splenic CD4⁺ T cells from mice immunized with nonreplicating immunogens like OVA or recombinant blood stage P. falciparum antigens, PfMSP-3 and PfMSP-1₁₉ or crude parasite antigen (PfAg) undergo sequential T cell activation, proliferation followed by activation-induced cell death (AICD) in a dose- and time-dependent manner after Ag restimulation. While PfMSP-3 and OVA-induced AICD was mediated through a death receptor-dependent apoptotic program, PfMSP-1₁₉ and PfAg-induced AICD was via a mechanism dependent on the activation of mitochondria apoptosis signalling pathway through Bax activation. These results provide insights into the mechanism through which two blood stage merozoite antigens trigger different apoptotic programs of AICD in splenic CD4⁺ T cells.