Shared reactivity of V{delta}2(neg) {gamma}{delta} T cells against cytomegalovirus-infected cells and tumor intestinal epithelial cells.
Long-lasting expansion of Vdelta2(neg) gammadelta T cells is a hallmark of cytomegalovirus (CMV) infection in kidney transplant recipients. The ligands of these cells and their role remain elusive. To better understand their immune function, we generated gammadelta T cell clones from several transplanted patients. Numerous patient Vdelta1(+), Vdelta3(+), and Vdelta5(+) gammadelta T cell clones expressing diverse Vgamma chains, but not control Vgamma9Vdelta2(+) T clones, displayed strong reactivity against CMV-infected cells, as shown by their production of tumor necrosis factor-alpha. Vdelta2(neg) gammadelta T lymphocytes could also kill CMV-infected targets and limit CMV propagation in vitro. Their anti-CMV reactivity was specific for this virus among herpesviridae and required T cell receptor engagement, but did not involve major histocompatibility complex class I molecules or NKG2D. Vdelta2(neg) gammadelta T lymphocytes expressed receptors essential for intestinal homing and were strongly activated by intestinal tumor, but not normal, epithelial cell lines. High frequencies of CMV- and tumor-specific Vdelta2(neg) gammadelta T lymphocytes were found among patients' gammadelta T cells. In conclusion, Vdelta2(neg) gammadelta T cells may play a role in protecting against CMV and tumors, probably through mucosal surveillance of cellular stress, and represent a population that is largely functionally distinct from Vgamma9Vdelta2(+) T cells.
Halary
Franck
F
UMR 5164, Centre National de la Recherche Scientifique, IFR 66, Université Bordeaux 2, 33076 Bordeaux, France.
Pitard
Vincent
V
Dlubek
Dorota
D
Krzysiek
Roman
R
de la Salle
Henri
H
Merville
Pierre
P
Dromer
Claire
C
Emilie
Dominique
D
Moreau
Jean-François
JF
Déchanet-Merville
Julie
J
D000951:Antigens, Neoplasm / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D002460:Cell Line; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D004847:Epithelial Cells / Q000276:immunology / Q000473:pathology; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor / Q000276:immunology; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor / Q000276:immunology; D005805:Genes, MHC Class I / Q000276:immunology; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D007414:Intestinal Neoplasms / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D016201:Receptors, Lymphocyte Homing / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000951:Antigens, Neoplasm; D000956:Antigens, Viral; D016692:Receptors, Antigen, T-Cell, gamma-delta; D016201:Receptors, Lymphocyte Homing; D014409:Tumor Necrosis Factor-alpha