Vaccine Elicited ASGM1+ CD8+ T Cells Are Essential for Protective Immunity Against Toxoplasma Gondii Infection

Abstract The importance of enriched asialylated sphingolipid GM1 (ASGM1) in CD8+ T cell dependent protective immunity against T. gondii infection is unknown. Using a vaccine challenge model of T. gondii infection, we observed treatment of animals with anti-ASGM1 resulted in 100% death and greater parasite burden at the site of infection. Upon further dissection of this phenotype, we found that anti-ASGM1 treatment depleted not only NK cells but also T cells in vaccinated mice. While both CD8+ and CD4+ T cells were affected, CD8+ T cells were more susceptible to the anti-ASGM1 treatment. ASGM1 on the surface of the T cells was expressed on a higher percentage of CD8+ T cells than CD4+ T cells. ASGM1 was highly enriched on the surface of memory CD8+ T cells (Tem and Tcm). However, Tem were more susceptible to anti-ASGM1 treatment. Anti-ASGM1 treatment during rechallenge resulted in greater depletion of activated CD8+ IFNγ+, Granzyme B+, Tem and Tef than Tcm cells. In addition, anti-ASGM1 depleted IFNγ+ CD4+ T cells. Recombinant IFNγ supplementation prolonged the survival of anti-ASGM1 treated mice, demonstrating that this antibody eliminated the protective T. gondii specific IFNγ-producing T cells important for control of the parasite. This study demonstrates that ASGM1 is enriched on effector T cells during T. gondii infection and the potential importance of changes in sialylation in lipid rafts for T cell activation during T. gondii infection.