Implication of γδ T cells in the human immune response to cytomegalovirus

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Abstract

In normal individuals, γδ T cells account for less than 6% of total peripheral T lymphocytes and mainly express T-cell receptor (TCR) Vδ2-Vγ9 chains. We have previously observed a dramatic expansion of γδ T cells in the peripheral blood of renal allograft recipients only when they developed cytomegalovirus (CMV) infection. This increase was long lasting (more than 1 year), was associated with an activation of γδ T cells, and concerned only Vδ1 or Vδ3 T-cell subpopulations. Analysis of γδ TCR junctional diversity revealed that CMV infection in these patients was accompanied by (a) a marked restriction of CDR3 size distribution in Vδ3 and, to a lesser extent, in Vδ1 chains; and (b) a selective expansion of Vδ1 cells bearing recurrent junctional amino acid motifs. These features are highly suggestive of an in vivo antigen-driven selection of γδ T-cell subsets during the course of CMV infection. Furthermore, Vδ1 and Vδ3 T cells from CMV-infected kidney recipients were able to proliferate in vitro in the presence of free CMV or CMV-infected fibroblast lysates but not uninfected or other herpes virus–infected fibroblast lysates. This in vitro expansion was inhibited by anti-γδ TCR mAb’s. These findings suggest that a population of γδ T cells might play an important role in the immune response of immunosuppressed patients to CMV infection.

Authors

Julie Déchanet, Pierre Merville, Annick Lim, Christelle Retière, Vincent Pitard, Xavier Lafarge, Susan Michelson, Claude Méric, Marie-Martine Hallet, Philippe Kourilsky, Luc Potaux, Marc Bonneville, Jean-François Moreau