Requirement of species-specific interactions for the activation of human gamma delta T cells by pamidronate.
Human gammadelta T cells bearing Vgamma2Vdelta2-TCR recognize various kinds of small nonpeptide Ags, and activation of them by a nitrogen-containing bisphosphonate Ag, pamidronate, requires Ag presentation by cells other than gammadelta T cells, including many human tumor cells. Present results demonstrated that tumor cell lines of nonhuman origins pulsed with pamidronate failed to activate human gammadelta T cells without exception, whereas most if not all human tumor cell lines could do so. Gammadelta T cells formed stable conjugates with pamidronate-pulsed human tumor cells and both conjugate formation and gammadelta T cell activation were inhibited significantly by anti-LFA-1 mAb, suggesting the requirement of LFA-1-mediated interaction with APC for efficient gammadelta T cell activation. Consistently, ICAM-1(low) tumor cell lines pulsed with pamidronate induced no or only weak activation of gammadelta T cells, whereas similarly treated ICAM-1(high) cell lines could activate them. One of the two ICAM-1(low) tumor cell lines pulsed with pamidronate induced strong gammadelta T cell activation after ICAM-1 gene transfer. However, another ICAM-1(low) human cell line as well as murine tumor cell lines pulsed with pamidronate remained totally defective in gammadelta T cell activation even after expression of human ICAM-1. These results suggested that activation of human gammadelta T cells by nonpeptide Ags required species-specific interactions in addition to LFA-1/ICAM-1-mediated cell adhesion with APC.
Kato
Yu
Y
Department of Immunology and Cell Biology, Kyoto University, Kyoto, Japan.
Tanaka
Yoshimasa
Y
Tanaka
Hidenori
H
Yamashita
Seiji
S
Minato
Nagahiro
N
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002415:Cats; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D002449:Cell Aggregation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D002645:Chickens; D018920:Coculture Techniques; D006224:Cricetinae; D004164:Diphosphonates / Q000494:pharmacology*; D004285:Dogs; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D051379:Mice; D018668:Muntjacs; D000077268:Pamidronate; D011817:Rabbits; D051381:Rats; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D013045:Species Specificity; D013552:Swine; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D004164:Diphosphonates; D016169:Lymphocyte Function-Associated Antigen-1; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018799:Intercellular Adhesion Molecule-1; D000077268:Pamidronate