Innate immunity to viruses: Control of vaccinia virus infection by gamma delta T cells

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.