Phenotypic profile and functional characterization of rat lymph node-derived gammadelta T cells: implication in the immune response to cytomegalovirus.
Gammadelta T cells are unique, and their localization at sites of infection is considered critical in immune defence. We demonstrate the accumulation of gammadelta T cells in rat regional popliteal lymph nodes (PLNi) starting 2 days after inoculation of cytomegalovirus (CMV) into the footpad. Early-appearance PLNi gammadelta T cells significantly inhibited plaque development and the spread of CMV infection. These gammadelta T cells were negative for CD4 and CD8beta receptors, proliferated in response to interleukin-2 (IL-2) and contained high levels of interferon-gamma (IFN-gamma), the appearance of which correlated with the curing of fibroblasts from virus infection. The addition of anti-IFN-gamma abolished the ability of fibroblast monolayers to be cured from CMV infection. In contrast, this protection was not abolished by the addition of anti-rat IL-2 or anti-rat TNF-alpha, or by the depletion of NKR-P1-bearing cells within gammadelta T cells. In addition, the present study shows that while gammadelta T cells derived from naive and CMV-infected rats are able to kill both YAC-1 targets and CMV-infected syngeneic fibroblasts in vitro, only the latter are able to clear CMV-infected fibroblast monolayers. Finally, our data suggest that the expression of NKR-P1 by gammadelta T cells is critical for cytotoxicity, but its contribution to the curing from CMV infection was limited.
Dyugovskaya
Larissa
L
Department of Immunology, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. larissa@techunix.ac.il
Hirsh
Mark
M
Ginsburg
Haim
H
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003586:Cytomegalovirus Infections / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology*; D051381:Rats; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D011994:Recombinant Proteins / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D016207:Cytokines; D007376:Interleukin-2; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011994:Recombinant Proteins