Innate immunity to viruses: control of vaccinia virus infection by gamma delta T cells.
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.
Selin
L K
LK
Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
Santolucito
P A
PA
Pinto
A K
AK
Szomolanyi-Tsuda
E
E
Welsh
R M
RM
D000818:Animals; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000032:analysis; D019674:Genes, T-Cell Receptor beta; D020022:Genetic Predisposition to Disease; D007111:Immunity, Cellular / Q000235:genetics; D007113:Immunity, Innate / Q000235:genetics; D007700:Kinetics; D008213:Lymphocyte Activation / Q000235:genetics; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D010529:Peritoneal Cavity / Q000166:cytology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D015996:Survival Rate; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014615:Vaccinia / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000821:virology*; D014616:Vaccinia virus / Q000276:immunology*; D014779:Virus Replication / Q000235:genetics / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D016692:Receptors, Antigen, T-Cell, gamma-delta