Comparison of cytolytic and proliferative activities of human gamma delta and alpha beta T cells from peripheral blood against various human tumor cell lines.
Peripheral blood lymphocytes (PBLs) from healthy donors were more than 95% enriched for gamma delta T cells. V gamma 9/V delta 2 was the predominant T-cell subset and represented more than two thirds of the isolated gamma delta T cells. When activated by surface-immobilized anti-TCR delta 1 monoclonal antibody (MoAb) during 5 days of culture, gamma delta T cells demonstrated a significant fourfold to 15-fold stronger cytolytic activity against various tumor cell lines than did PBL polyclonal alpha beta T cells analogously activated by surface-immobilized anti-CD3 MoAbs. Blocking experiments with specific MoAbs demonstrated that the cytolytic activity of gamma delta T cells was non-major histocompatibility complex (MHC) restricted and did not involve the gamma delta T-cell antigen receptor (TCR) but that cytolytic activity was dependent on LFA-1 beta/ICAM1 interaction. The proliferative responses of gamma delta and alpha beta T cells to Ovcar-3 tumor cells and irradiated allogeneic PBLs were inhibited by anti-HLA-A,B,C MoAb. Our findings suggest that gamma delta T cells activated via the TCR have a significant advantage in non-MHC-restricted lysis of various tumor cell lines over PBL alpha beta T cells stimulated analogously with anti-CD3, which may be important in terms of applicability of activated gamma delta cells for adoptive immunotherapy of metastatic cancers.
Laboratory of Immunology, Sansum Medical Research Foundation, Santa Barbara, Calif. 93105.
A S
AS
Ensslin
B
B
Formby
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D015395:Histocompatibility Antigens Class I / Q000502:physiology; D006801:Humans; D016130:Immunophenotyping; D007167:Immunotherapy; D018799:Intercellular Adhesion Molecule-1; D015979:Killer Cells, Lymphokine-Activated / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D009369:Neoplasms / Q000628:therapy*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D015395:Histocompatibility Antigens Class I; D016169:Lymphocyte Function-Associated Antigen-1; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018799:Intercellular Adhesion Molecule-1