Uncoupling between immunological synapse formation and functional outcome in human gamma delta T lymphocytes.
Human T lymphocytes expressing the Vgamma9Vdelta2 TCR recognize non-peptidic Ags, referred to as phosphoantigens, produced by microbial pathogens and by human tumor cells. Here we show that gammadelta T cells establish a mature immunological synapse (IS) with the myelomonocytic THP-1 tumoral cell line. This synapse is characterized by an enrichment for phosphotyrosine, CD2, and gammadelta TCR together with the exclusion of CD45. The CD94 and NKG2D receptors are also recruited to the signaling area, while the C-lectin-like activation marker CD69 segregates out of the synapse. gammadelta T cell conjugation to THP-1 increases upon stimulation by soluble phosphoantigen, is paralleled by the metabolic activation of gammadelta T cells and leads to cytokine production. Molecular segregation of the above molecules also occurs at the gammadelta T cell/THP-1 interface in the absence of exogenously added phosphoantigen, although it does not result in intracellular signaling and cytokine production under these conditions. Hence the molecular interactions at the gammadelta T cell-THP-1 target cell interface are sufficient to induce the formation of an IS, but cytokine production requires the full engagement of gammadelta TCR by a strong agonist. Thus in gammadelta T cells, formation of the IS is uncoupled from its functional outcome.
Favier
Benoit
B
Department of Immunology, Unité 563, Institut National de la Santé et de la Recherche Médicale, Centre Hospitalier Universitaire de Purpan, Toulouse, France.
Espinosa
Eric
E
Tabiasco
Julie
J
Dos Santos
Cédric
C
Bonneville
Marc
M
Valitutti
Salvatore
S
Fournié
Jean-Jacques
JJ
D000941:Antigens / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D015415:Biomarkers; D002449:Cell Aggregation / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D011756:Diphosphates / Q000494:pharmacology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051920:NK Cell Lectin-Like Receptor Subfamily D; D055655:NK Cell Lectin-Like Receptor Subfamily K; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism* / Q000502:physiology; D011971:Receptors, Immunologic / Q000378:metabolism; D055607:Receptors, Natural Killer Cell; D015398:Signal Transduction / Q000276:immunology; D012995:Solubility; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D000099192:CD69 Antigens
D000941:Antigens; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015415:Biomarkers; D016207:Cytokines; D011756:Diphosphates; D015395:Histocompatibility Antigens Class I; D037181:Lectins, C-Type; D051920:NK Cell Lectin-Like Receptor Subfamily D; D055655:NK Cell Lectin-Like Receptor Subfamily K; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D000099192:CD69 Antigens; C497869:KLRD1 protein, human; C527085:KLRK1 protein, human; C099187:MHC class I-related chain A; C429553:bromohydrin pyrophosphate