EVIDENCE FOR CD8(-CELL IMMUNITY TO MURINE ROTAVIRUS IN THE ABSENCE OFPERFORIN, FAS, AND GAMMA-INTERFERON() T)

We recently showed that class I-restricted CD8(+) T cells mediate clea rance of primary rotavirus infection in mice: J(H)D knockout (J(H)D -/ -) (B-cell-deficient) mice depleted of CD8(+) T cells become chronical ly infected with murine rotavirus, and beta(2), microglobulin knockout (beta(2) m -/-) mice have delayed but complete clearance of primary r otavirus infection. In the present work we have analyzed the mechanism used by CD8(+) T cells to clear rotavirus infection. We first determi ned that perforin knockout (perforin -/-) mice and lpr (fas-deficient) mice clear rotavirus infection with the same kinetics as control mice . When perforin -/- or perforin +/+ mice were depleted of CD8(+) T cel ls by administration of an anti-CD8 monoclonal antibody, they showed a delay of 1 to 2 days in the clearance of rotavirus infection compared to the clearance time for untreated control mice, indicating that CD8 (+) T cells in both groups of mice participate in the resolution of pr imary rotavirus infection. In addition, passively transferred CD8(+) T cells from rotavirus-infected perforin +/+ and perforin -/- mice were able to mediate viral clearance in Rag 2 knockout (Rag 2 -/-) mice ch ronically infected with rotavirus with similar kinetics, suggesting th at CD8(+) T cells from perforin -/- mice are as efficient as CD8(+) T cells from perforin +/+ mice in clearing a rotavirus infection. Gamma interferon (IFN-gamma) was also shown to be unnecessary for the antiro tavirus effect of CD8(+) T cells: IFN-gamma knockout (IFN-gamma -/-) m ice and J(H)D -/-, perforin -/-, and perforin +/+ mice depleted of IFN -gamma by administration of an anti-IFN-gamma monoclonal antibody clea red rotavirus infection with the same kinetics as those for control mi ce. Hence, CD8(+) T cells have an antirotaviral effect that is not med iated by perforin and appears to be independent of fas and the release of IFN-gamma.