Vγl⁺ γδ T cells play protective roles at an early phase of murine cytomegalovirus infection through production of interferon-γ

Cytomegalovirus (CMV) causes severe opportunistic infection in immunocompromised hosts. The importance of conventional αβ T cells in protection against CMV infection has been well documented. However, the role of the second T-cell population (which express the γδ T-cell receptor) in CMV infection is not known. In the present study, we analysed the function and protective role of γδ T cells in a murine cytomegalovirus (MCMV) infection model. After intraperitoneal infection with MCMV, the number of γδ T cells increased in the liver and peritoneal cavity from day 3, and reached a peak on day 5. The γδ T cells showed an activated T-cell phenotype and predominantly expressed Vγ1, which is known to be expressed by heat-shock protein 65 (hsp 65)-specific γδ T cells. Analysis of cytokine expression demonstrated that the MCMV-induced γδ T cells expressed interferon-γ (IFN-γ) and tumour necrosis factor-α (TNF-α) but not interleukin-4 (IL-4), implying their participation in the cell-mediated immune response against MCMV. Depletion of γδ T cells by anti-TT-cell receptor (TCR) γδ monoclonal antibody (mAb) treatment resulted in significant increase of virus titre and decrease of IFN-γ in the liver on day 3 after MCMV infection, which further supports the importance of γδ T cells in early protection against infection. Finally, the MCMV-induced γδ T cells produced IFN-γ in vitro in response to hsp 65. Our results suggest that γδ T cells participate in early protection against MCMV infection through recognition of hsp 65 and production of IFN-γ.