Implication of gamma delta T cells in the human immune response to cytomegalovirus

In normal individuals, gamma delta T cells account for less than 6% of tota l peripheral T lymphocytes and mainly express T-cell receptor (TCR) V delta 2-V gamma 9 chains. We have previously observed a dramatic expansion of ga mma delta T cells in the peripheral blood of renal allograft recipients onl y when they developed cytomegalovirus (CMV) infection, This increase was lo ng lasting (more than 1 year), was associated with an activation of gamma d elta T cells, and concerned only V delta 1 or V delta 3 T-cell subpopulatio ns. Analysis of gamma delta TCR junctional diversity revealed that CMV infe ction in these patients was accompanied by (a) a marked restriction of CDR3 size distribution in V delta 3 and, to a lesser extent, in V delta 1 chain s; and (b) a selective expansion of V delta 1 cells bearing recurrent junct ional amino acid motifs. These features are highly suggestive of an in vivo antigen-driven selection of gamma delta T-cell subsets during the course o f CMV infection, Furthermore, V delta 1 and V delta 3 T cells from CMV-infe cted kidney recipients were able to proliferate in vitro in the presence of free CMV or CMV-infected fibroblast lysates but not uninfected or other he rpes virus-infected fibroblast lysates, This in vitro expansion was inhibit ed by anti-gamma delta TCR mAb's, These findings suggest that a population of gamma delta T cells might play an important role in the immune response of immunosuppressed patients to CMV infection.