Characterization of IL-2-induced murine cells which exhibit ADCC activity.
The incubation of murine splenocytes in recombinant interleukin 2 (IL-2) gives rise to both lymphokine-activated killer (LAK) cells capable of lysing fresh tumor cells and cells capable of mediating antibody-dependent cellular cytotoxicity (ADCC) in the presence of anti-H2 allosera. A similarity between these two IL-2-induced cell populations was found. The precursors of the cells mediating these activities were shown to be ASGM1 positive, Thy 1 negative, and radiosensitive. Cells taken from the spleen, thymus, and bone marrow were able to mediate ADCC after culture in IL-2. The effector cell was either Thy 1 positive or negative and was less affected by anti-Thy 1 plus C' treatment than cells which mediated LAK activity. In addition ADCC was exhibited in IL-2-cultured splenocytes from various murine strains and correlated with their LAK activity with one exception. While IL-2-cultured C57BL/6 splenocytes exhibited LAK activity similar to that of C3H LAK cells, no ADCC activity could be demonstrated in C57BL/6 cells. Study of the difference in the ability of these two strains to mediate ADCC revealed that IL-2-induced FcR+ cells in C3H thymocytes, but not in C57BL/6 thymocytes. Based on FACS analysis and on the radiosensitivity of the induction of both FcR+ cells and ADCC, it was suggested that IL-2 was expanding a small FcR+ cell population rather than inducing an increase in FcR density on the cell surface. The relationship between the IL-2-induced ADCC mediator and other IL-2-induced cells, as well as ADCC effector cells, and the possible implications of the results for the in vivo therapy of cancer based on ADCC are discussed.
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D000954:Antigens, Surface / Q000032:analysis / Q000276:immunology; D001212:Asialoglycoproteins / Q000032:analysis; D007111:Immunity, Cellular / Q000528:radiation effects; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000145:classification / Q000276:immunology* / Q000528:radiation effects; D008214:Lymphocytes / Q000145:classification / Q000276:immunology*; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D011961:Receptors, Fc / Q000032:analysis*; D018800:Thy-1 Antigens
D000954:Antigens, Surface; D001212:Asialoglycoproteins; D007376:Interleukin-2; D011961:Receptors, Fc; D018800:Thy-1 Antigens