CD2-mediated IL-12–dependent signals render human γδ-T cells resistant to mitogen-induced apoptosis, permitting the large-scale ex vivo expansion of functionally distinct lymphocytes: implications for the development of adoptive immunotherapy strategies

摘要: The ability of human gamma delta-T cells to mediate a number in vitro functions, including innate antitumor and antiviral activity, suggests these can be exploited selected examples adoptive immunotherapy. To date, however, studies examine such issues on clinical scale have not been possible, owing large measure the difficulty obtaining sufficient numbers viable given their relative infrequency readily available tissues. Standard methods used expand T often use combination mitogens, as anti-T-cell receptor antibody OKT3 interleukin (IL)-2. These stimuli, though promoting expansion alpha beta-T cells, usually do promote efficient cells. CD2-mediated, IL-12-dependent signals that result selective from cultures mitogen-stimulated peripheral blood mononuclear are identified. It is first established exquisitely sensitive apoptosis induced by T-cell mitogens IL-2. Next it shown CD2-mediated signals, which lead so selectively protecting subsets mitogen-induced apoptosis. Finally, demonstrated apoptosis-resistant capable mediating significant cytotoxicity against panel human-derived tumor cell lines vitro. Both biologic practical implications resistance considered discussed because findings may play role development new forms cellular (Blood. 2000;96:3827-3837)