Abstract

Using vaccine challenge model of T. gondii infection, we found that treatments with two commonly used for NK cell depletion antibodies resulted in different survival outcomes during secondary infection. Anti-ASGM1 resulted in 100% death and greater parasite burden at the site of infection than anti-NK1.1. Anti-NK1.1 treatment resulted in increased parasite burdens, but animals did not die. Further we found that anti-ASGM1 treatment depleted T cells. CD8+ T cells were more susceptible that CD4+ T cells to the treatment. ASGM1 was expressed on a higher percentage of CD8+ T cells than CD4+ T cells and CD8+ T cells. In T. gondii-immunized animals ASGM1 was enriched on effector memory (Tem) and central memory (Tcm) CD8+ T cells. However, Tem were more susceptible to the treatment. After secondary infection, Tem, Tcm, effector (Tef) and naive (Tn) CD8+ T cells were positive for ASGM1. Anti-ASGM1 treatment during reinfection resulted in greater depletion of activated IFN{gamma}+, Granzyme B+, Tem and Tef than Tcm and Tn CD8+ T cells. Anti-ASGM1 also depleted IFN{gamma}+ CD4+ T cells. Recombinant IFN{gamma} supplementation prolonged survival of anti-ASGM1 treated mice, demonstrating that this antibody eliminated IFN{gamma}-producing T and NK cells important for control of the parasite. These results highlight that anti-ASGM1 antibody is not an optimal choice for targeting only NK cells and more precise approaches should be used. This study uncovers ASGM1 as a marker of activated effector T cells and the potential importance of changes in sialylation in lipid rafts for T cell activation during T. gondii infection.