The existence of gamma delta T cells has been known for over 15 years, but
their significance in Innate immunity to virus infections has not been dete
rmined. We show here that gamma delta T cells are well suited to provide a
rapid response to virus infection and demonstrate their role in innate resi
stance to vaccinia virus (VV) infection in both normal C57BL/6 and beta TCR
knockout (KO) mice. VV-infected mice deficient in gamma delta T cells had
significantly higher VV titers early postinfection (PI) and increased morta
lity when compared with control mice. There was a rapid and profound VV-ind
uced increase in IFN-gamma -producing gamma delta T cells In the peritoneal
cavity and spleen of VV-infected mice beginning as early as day 2 PI. This
rapid response occurred in the absence of priming, as there was constituti
vely a significant frequency of VV-specific gamma delta T cells in the sple
en in uninfected beta TCR KO mice, as demonstrated by limiting dilution ass
ay. Also, like NK cells, another mediator of innate immunity to viruses, ga
mma delta T cells in uninfected beta TCR KO mice expressed constitutive cyt
olytic activity. This cytotoxicity was enhanced and included a broader rang
e of targets after VV infection. VV-infected beta TCR KO mice cleared most
of the virus by day 8 PI, the peak of the gamma delta T cell response, but
thereafter the gamma delta T cell number declined and the virus recrudeseed
. Thus, gamma delta T cells can be mediators of innate immunity to viruses,
having a significant impact on virus replication early in infection in the
presence or absence of the adaptive immune response.