Regulation of gammadelta T cell survival by soluble HLA-I: involvement of CD8 and activating killer Ig-like receptors.
We show that human Vdelta1 or Vdelta2 T lymphocytes secrete FasL and undergo apoptosis upon incubation with soluble HLA (sHLA)-I or after cross-linking of CD8, with a kinetics different from that observed following ligation of TCR. sHLA-I-induced apoptosis was blocked by anti-CD8 mAb; on the other hand, sHLA-I was not effective in CD8- clones, while an HLA-I mutated in the alpha3 domain, responsible for CD8 binding, was not functional on CD8+ clones. Purified sHLA-Cw3 or -Cw4 alleles, isolated from the Cw3- or Cw4-transfected 721.221 lymphoblastoid cell line, triggered gammadelta T cell apoptosis, interacting with the specific receptors CD158j/KIR2DS2 or CD158 h/KIR2DS1, respectively, also known as activating isoforms of killer Ig-like receptors (KIR). Again, this effect was dependent on FasL secretion and it was blocked by specific mAb to KIR2DS2 or KIR2DS1. The engagement of CD8 or activating KIR also triggered the production of TNF-alpha. Noteworthy, sHLA-I molecules synergize with antigen-mediated activation of Vdelta2 T cells: Indeed, Vdelta2 T lymphocytes produced TNF-alpha when stimulated with isopentenyl pyrophosphate, and this effect was enhanced by sHLA-I. These findings suggest that sHLA-I can regulate gammadelta T cell survival and that activating KIR may amplify antigen-specific Vdelta2 T cell responses.
Poggi
Alessandro
A
Laboratory of Experimental Oncology D, National Institute for Cancer Research, Genoa, Italy. alessandro.poggi@istge.it
Contini
Paola
P
Catellani
Silvia
S
Setti
Maurizio
M
Murdaca
Giuseppe
G
Zocchi
Maria Raffaella
MR
D000483:Alleles; D017209:Apoptosis / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002470:Cell Survival / Q000276:immunology; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology; D054340:Receptors, KIR; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology; D019014:fas Receptor / Q000276:immunology
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D015395:Histocompatibility Antigens Class I; C433932:KIR2DS2 protein, human; D008562:Membrane Glycoproteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor