Circumsporozoite Protein-Specific K d -Restricted CD8+ T Cells Mediate Protective Antimalaria Immunity in Sporozoite-Immunized MHC-I- K d Transgenic Mice

Abstract EN

Although the roles of CD8+ T cells and a major preerythrocytic antigen, the circumsporozoite (CS) protein, in contributing protective antimalaria immunity induced by radiation-attenuated sporozoites, have been shown by a number of studies, the extent to which these players contribute to antimalaria immunity is still unknown.

To address this question, we have generated C57BL/6 (B6) transgenic (Tg) mice, expressing K d molecules under the MHC-I promoter, called MHC-I- K d -Tg mice.

In this study, we first determined that a single immunizing dose of IrPySpz induced a significant level of antimalaria protective immunity in MHC-I- K d -Tg mice but not in B6 mice.

Then, by depleting various T-cell subsets in vivo, we determined that CD8+ T cells are the main mediator of the protective immunity induced by IrPySpz.

Furthermore, when we immunized (MHC-I- K d -Tg × CS-Tg) F1 mice with IrPySpz after crossing MHC-I- K d -Tg mice with PyCS-transgenic mice (CS-Tg), which are unable to mount PyCS-specific immunity, we found that IrPySpz immunization failed to induce protective antimalaria immunity in (MHC-I- K d -Tg × CS-Tg) F1 mice, thus indicating the absence of PyCS antigen-dependent immunity in these mice.

These results indicate that protective antimalaria immunity induced by IrPySpz in MHC-I- K d -Tg mice is mediated by CS protein-specific, K d -restricted CD8+ T cells.