Antibody-dependent anti-cytomegalovirus activity of human γδ T cells expressing CD16 (FcγRIIIa)

Human cytomegalovirus (HCMV) infection is an important cause of morbidity and mortality in transplant recipients. Long-term protective immunity against HCMV requires both sustained specific T-cell response and neutralizing IgG production, but the interplay between these effector arms remains poorly defined. We previously demonstrated that gamma delta T cells play a substantial role as anti-HCMV T-cell effectors. The observation that CD16 (Fc gamma RIIIA) was specifically expressed by the majority of HCMV-induced gamma delta T cells prompted us to investigate their cooperation with anti-HCMV IgG. We found that CD16 could stimulate gamma delta T cells independently of T-cell receptor (TCR) engagement and provide them with an intrinsic antibody-dependent cell-mediated cytotoxic (ADCC) potential. Although CD16(+) gamma delta T cells did not mediate ADCC against HCMV-infected cells, in accordance with the low level of anti-HCMV IgGs recognizing infected cells, they produced IFN gamma when incubated with IgG-opsonized virions. This CD16-induced IFN gamma production was greatly enhanced by IL12 and IFN gamma, 2 cytokines produced during HCMV infection, and conferred to gamma delta T cells the ability to inhibit HCMV multiplication in vitro. Taken together, these data identify a new antiviral function for gamma delta T cells through cooperation with anti-HCMV IgG that could contribute to surveillance of HCMV reactivation in transplant recipients. (Blood. 2012; 119(6): 1418-1427)