Phenotypic and Functional Characterization of Human γδ T-Cell Subsets in Response to Influenza A Viruses

Like alpha beta T cells, human gamma delta T cells also have different subsets with distinct characteristics. Whether human V gamma 9V delta 2 T cells have functionally different subsets in response to influenza A (fluA) viruses remains unknown. In this study, we show for the first time that both central (CD45RA(-)CD27(+)) and effector (CD45RA(-)CD27(-)) memory V gamma 9V delta 2 T cells have similar levels of immediate interferon (IFN) gamma and cytotoxic responses to human and avian fluA virus-infected cells. In contrast, CD56(+) V gamma 9V delta 2 T cells have significantly higher cytotoxicity against fluA virus-infected cells compared with their CD56(-) counterparts, whereas both subsets have similar IFN-gamma responses. We further demonstrate that the CD16-dependent degranulation pathway, but not antibody-dependent cell-mediated cytotoxicity, contribute to the superior cytotoxicity of CD56(+) V gamma 9V delta 2 T cells. Our study provides further evidence for the phenotypic and functional characterization of human V gamma 9V delta 2 T-cell subsets during fluA virus infection and may help improve the gamma delta T-cell-based immunotherapy for viral infection.