Innate immunity to viruses: control of vaccinia virus infection by gamma delta T cells
Department of Pathology
Animals; Cell Movement; Cytotoxicity Tests, Immunologic; Cytotoxicity, Immunologic; Epitopes, T-Lymphocyte; Genes, T-Cell Receptor beta; Genetic Predisposition to Disease; Immunity, Cellular; Immunity, Natural; Kinetics; Lymphocyte Activation; Lymphocyte Count; Lymphocyte Depletion; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, SCID; Peritoneal Cavity; Receptors, Antigen, T-Cell, gamma-delta; Survival Rate; T-Lymphocyte Subsets; T-Lymphocytes, Cytotoxic; Vaccinia; Vaccinia virus; Virus Replication
Life Sciences | Medicine and Health Sciences
The existence of gammadelta T cells has been known for over 15 years, but their significance in innate immunity to virus infections has not been determined. We show here that gammadelta T cells are well suited to provide a rapid response to virus infection and demonstrate their role in innate resistance to vaccinia virus (VV) infection in both normal C57BL/6 and beta TCR knockout (KO) mice. VV-infected mice deficient in gammadelta T cells had significantly higher VV titers early postinfection (PI) and increased mortality when compared with control mice. There was a rapid and profound VV-induced increase in IFN-gamma-producing gammadelta 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 constitutively a significant frequency of VV-specific gammadelta T cells in the spleen in uninfected beta TCR KO mice, as demonstrated by limiting dilution assay. Also, like NK cells, another mediator of innate immunity to viruses, gammadelta T cells in uninfected beta TCR KO mice expressed constitutive cytolytic activity. This cytotoxicity was enhanced and included a broader range of targets after VV infection. VV-infected beta TCR KO mice cleared most of the virus by day 8 PI, the peak of the gammadelta T cell response, but thereafter the gammadelta T cell number declined and the virus recrudesced. Thus, gammadelta 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.
DOI of Published Version
J Immunol. 2001 Jun 1;166(11):6784-94.
Journal of immunology (Baltimore, Md. : 1950)
Selin, Liisa K.; Santolucito, Paul A.; Pinto, Amelia K.; Szomolanyi-Tsuda, Eva; and Welsh, Raymond M., "Innate immunity to viruses: control of vaccinia virus infection by gamma delta T cells" (2001). Open Access Articles. 1127.