Vgamma1+ gammadelta T cells play protective roles at an early phase of murine cytomegalovirus infection through production of interferon-gamma.
Cytomegalovirus (CMV) causes severe opportunistic infection in immunocompromised hosts. The importance of conventional alphabeta T cells in protection against CMV infection has been well documented. However, the role of the second T-cell population (which express the gammadelta T-cell receptor) in CMV infection is not known. In the present study, we analysed the function and protective role of gammadelta T cells in a murine cytomegalovirus (MCMV) infection model. After intraperitoneal infection with MCMV, the number of gammadelta T cells increased in the liver and peritoneal cavity from day 3, and reached a peak on day 5. The gammadelta T cells showed an activated T-cell phenotype and predominantly expressed Vgamma1, which is known to be expressed by heat-shock protein 65 (hsp 65)-specific gammadelta T cells. Analysis of cytokine expression demonstrated that the MCMV-induced gammadelta T cells expressed interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) but not interleukin-4 (IL-4), implying their participation in the cell-mediated immune response against MCMV. Depletion of gammadelta T cells by anti-T-cell receptor (TCR) gammadelta monoclonal antibody (mAb) treatment resulted in significant increase of virus titre and decrease of IFN-gamma in the liver on day 3 after MCMV infection, which further supports the importance of gammadelta T cells in early protection against infection. Finally, the MCMV-induced gammadelta T cells produced IFN-gamma in vitro in response to hsp 65. Our results suggest that gammadelta T cells participate in early protection against MCMV infection through recognition of hsp 65 and production of IFN-gamma.
Ninomiya
T
T
Departments of Immunology, Kyushu University, Fukuoka, Japan.
Takimoto
H
H
Matsuzaki
G
G
Hamano
S
S
Yoshida
H
H
Yoshikai
Y
Y
Kimura
G
G
Nomoto
K
K
D000818:Animals; D001426:Bacterial Proteins; D018834:Chaperonin 60; D018833:Chaperonins / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006566:Herpesviridae Infections / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000821:virology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018146:Muromegalovirus / Q000254:growth & development; D010529:Peritoneal Cavity / Q000473:pathology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology
D001426:Bacterial Proteins; D018834:Chaperonin 60; D016207:Cytokines; D016692:Receptors, Antigen, T-Cell, gamma-delta; C074119:heat-shock protein 65, Mycobacterium; D018664:Interleukin-12; D007371:Interferon-gamma; D018833:Chaperonins