Augmentation by anti-T3 antibody of the lymphokine-activated killer cell-mediated cytotoxicity.
This study showed that a mAb (145-2C11) against the T3 epsilon-chain of the TCR complex augmented the cytotoxic activity of the lymphokine-activated killer (LAK) effectors. The LAK cells were induced by culturing normal spleen cells with purified human rIL-2. Adding alpha T3 at the effector phase of the cytotoxic reactions augmented the LAK-mediated cytotoxicity. The alpha T3-augmented LAK killing was seen only with tumor targets, and there was no increase of killing against Con A-induced lymphoblasts. The augmentation effect was dose dependent on both the amounts of alpha T3 and the number of LAK cells added. A very low concentration of alpha T3 (1/10,000 dilution of culture supernatants) was sufficient to induce alpha T3-augmented LAK-mediated cytotoxicity. Human rIL-2 at 10 to 30 U/ml was sufficient to generate LAK cells for maximal alpha T3 augmentation, whereas 300 to 1000 U/ml of IL-2 were needed to generate maximal LAK activity when tested in the absence of alpha T3. LAK cells generated for longer periods of time showed a progressive increase of alpha T3-augmented cytotoxicity. For some targets, the alpha T3-augmented LAK killing was FcR dependent as evidenced by the ability of alpha FcR mAb 2.4G2 to inhibit, and for others it was not inhibited. The alpha T3-augmented killing did not correlate with the FcR expression on target cells as defined by 2.4G2. The LAK cells were both Lyt-2+ and Lyt-2-, but the LAK cells involved in alpha T3-augmented killing were exclusively Lyt-2+. Preincubation of LAK cells with alpha T3, but not preincubation of targets with alpha T3, resulted in augmented killing suggesting that the alpha T3 effect was unrelated to an antibody-dependent cell-mediated cytotoxicity. Our findings indicate that alpha T3 is a potent reagent to augment the cytotoxic reaction of LAK cells. These results suggested that a relationship might exist between the T3 complex and the cytotoxic activity of a subpopulation of Lyt-2+ LAK cells.
Ting
C C
CC
Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892.
Hargrove
M E
ME
Yun
Y S
YS
D000276:Adjuvants, Immunologic / Q000502:physiology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007694:Killer Cells, Natural / Q000145:classification / Q000276:immunology*; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010641:Phenotype; D011961:Receptors, Fc / Q000032:analysis; D013154:Spleen / Q000166:cytology; D013997:Time Factors
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D008222:Lymphokines; D011961:Receptors, Fc