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-1(19) 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-1(19) 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.

Cellular and humoral immune responses against the Plasmodium vivax MSP-119 malaria vaccine candidate in individuals living in an endemic area in north-eastern Amazon region of Brazil

“…Low proliferative responses in the presence of MSP-1 19 of P. falciparum and Plasmodium chabaudi chabaudi have already been demonstrated [37,38]. The results also showed a low proliferative response against PSS1 crude antigen or PvMSP-1 19 after 96 h culture.…”

Heterogeneous and Tissue-Specific Regulation of Effector T Cell Responses by IFN-γ during Plasmodium berghei ANKA Infection

“…Importantly, however, the contribution of modified migratory behaviour following treatment with anti-IFN- γ leading to changes in splenic T cell numbers was not addressed. In separate studies, Ag-specific T cell apoptosis has been shown to occur during malaria infection through distinct death receptor- and bax-dependent pathways (37).…”

Immune Activation and Regulation in Simian Immunodeficiency Virus-Plasmodium fragile-Coinfected Rhesus Macaques

“…Thus, both P. fragile and SIV infection contributed to enhanced immune activation in coinfected animals. We predict that the increased load of both SIV and malaria antigens exacerbates the chronic immune activation that is a hallmark of HIV and SIV infection (29,31,66,67) and will prevent the development of effective antimalaria immunity, because an immunoregulatory response is necessary to sustain a chronic malaria infection and to develop partial immunity to future reinfections with malaria (19,20,68,69). More detailed studies are needed to define which effects on chronic immune stimulation in coinfection are specific for parasite versus viral antigens.…”