Comparison of cytolytic and proliferative activities of human gamma delta and alpha beta T cells from peripheral blood against various human tumor cell lines.

Abstract

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.