Evidence for CD8+ T-cell immunity to murine rotavirus in the absence of perforin, fas, and gamma interferon.
We recently showed that class I-restricted CD8+ T cells mediate clearance of primary rotavirus infection in mice: JHD knockout (JHD -/-) (B-cell-deficient) mice depleted of CD8+ T cells become chronically infected with murine rotavirus, and beta2 microglobulin knockout (beta2m -/-) mice have delayed but complete clearance of primary rotavirus infection. In the present work we have analyzed the mechanism used by CD8+ T cells to clear rotavirus infection. We first determined 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 cells 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 primary 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 chronically infected with rotavirus with similar kinetics, suggesting that 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 antirotavirus effect of CD8+ T cells: IFN-gamma knockout (IFN-gamma -/-) mice and JHD -/-, perforin -/-, and perforin +/+ mice depleted of IFN-gamma by administration of an anti-IFN-gamma monoclonal antibody cleared rotavirus infection with the same kinetics as those for control mice. Hence, CD8+ T cells have an antirotaviral effect that is not mediated by perforin and appears to be independent of fas and the release of IFN-gamma.
Franco
M A
MA
Department of Medicine, Stanford University School of Medicine, California 94305, USA. francoma@leland.stanford.edu
Tin
C
C
Rott
L S
LS
VanCott
J L
JL
McGhee
J R
JR
Greenberg
H B
HB
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D004268:DNA-Binding Proteins; D005260:Female; D017353:Gene Deletion; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D008212:Lymphocyte Depletion; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011506:Proteins / Q000235:genetics / Q000276:immunology*; D012401:Rotavirus / Q000276:immunology*; D012400:Rotavirus Infections / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D004268:DNA-Binding Proteins; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D011506:Proteins; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; D054353:Perforin; D007371:Interferon-gamma