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

• Published in: The Journal of clinical investigation Vol. 103; no. 10; pp. 1437 - 1449
• Main Authors: Déchanet, J, Merville, P, Lim, A, Retière, C, Pitard, V, Lafarge, X, Michelson, S, Méric, C, Hallet, M M, Kourilsky, P, Potaux, L, Bonneville, M, Moreau, J F
• Format: Journal Article
• Language: English
• Published: United States 15.05.1999
• Subjects: Adolescent; Adult; Amino Acid Sequence; Base Sequence; Child; Cytomegalovirus - immunology; Cytomegalovirus Infections - etiology; Cytomegalovirus Infections - immunology; DNA Primers - genetics; Female; Humans; In Vitro Techniques; Kidney Transplantation - adverse effects; Kidney Transplantation - immunology; Lymphocyte Activation; Male; Middle Aged; Molecular Sequence Data; Receptors, Antigen, T-Cell, gamma-delta - genetics; Receptors, Antigen, T-Cell, gamma-delta - metabolism; T-Lymphocyte Subsets - immunology; Time Factors
• ISSN: 0021-9738; 1558-8238

In normal individuals, gammadelta T cells account for less than 6% of total peripheral T lymphocytes and mainly express T-cell receptor (TCR) Vdelta2-Vgamma9 chains. We have previously observed a dramatic expansion of gammadelta 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 gammadelta T cells, and concerned only Vdelta1 or Vdelta3 T-cell subpopulations. Analysis of gammadelta TCR junctional diversity revealed that CMV infection in these patients was accompanied by (a) a marked restriction of CDR3 size distribution in Vdelta3 and, to a lesser extent, in Vdelta1 chains; and (b) a selective expansion of Vdelta1 cells bearing recurrent junctional amino acid motifs. These features are highly suggestive of an in vivo antigen-driven selection of gammadelta T-cell subsets during the course of CMV infection. Furthermore, Vdelta1 and Vdelta3 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-gammadelta TCR mAb's. These findings suggest that a population of gammadelta T cells might play an important role in the immune response of immunosuppressed patients to CMV infection.