Human gammadelta-T cells in adoptive immunotherapy of malignant and infectious diseases.
Human gammadelta-T cells are capable of mediating both innate antitumor and antiviral activity, functions that theoretically might be exploitable in the treatment of a variety of malignant or infectious diseases. Nonetheless, experimental therapies incorporating the adoptive transter of human gammadelta-T cells have remained unfeasible to date owing largely to the difficulty of isolating or expanding sufficient numbers of gammadelta-T cells. It is in this context that recent discoveries from our laboratory are presented. By identifying specific signaling pathways that selectively inhibit activation-induced apoptosis in apoptosis-prone gammadelta-T cells, we have been able to expand large numbers of viable and functional human gammadelta-T cells, an undertaking until now notpossible. As important, these apoptosis-resistant gammadelta-Tcells appear to retain major histocompatibility complex-unrestricted (innate) antitumor activity against a wide variety of human tumor cells both in vitro and in vivo. Moreover, apoptosis-resistant gammadelta-T cells also display potent innate antiviral activity in vitro against human immunodeficiency virus-1. Both the biologic and practical implications of these findings are considered and discussed particularly as they relate to the development of future adoptive immunotherapy strategies.
Lopez
Richard D
RD
Bone Marrow Transplantation Program, University of Alabama at Birmingham, 35294-3300, USA. richard.lopez@ccc.uab.edu
D017209:Apoptosis; D018801:CD2 Antigens / Q000378:metabolism; D003141:Communicable Diseases / Q000276:immunology / Q000628:therapy; D015658:HIV Infections / Q000276:immunology / Q000628:therapy; D015497:HIV-1; D006801:Humans; D016219:Immunotherapy, Adoptive; D018664:Interleukin-12 / Q000378:metabolism; D018448:Models, Immunological; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*
D018801:CD2 Antigens; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018664:Interleukin-12