Specific triggering of gamma, delta T cells by K562 activates the gamma, delta T cell receptor and may regulate natural killer-like function.
Freshly isolated and resting gamma/delta T cell lines, although capable of lysing a variety of MHC-unrestricted targets, fail to lyse K562. Yet, the killing of K562 can be specifically induced by antibodies to CD3 or delta-chains. Although this phenomenon may be caused by redirected lysis, it also raised the possibility that K562 may possess ligands capable of specifically interacting with the gamma/delta receptor. We found that K562 specifically induced both CD3 and delta modulation as well as IL-2R expression and IL-2 production by gamma/delta cells, supporting the idea that the TCR-gamma/delta is specifically triggered by K562 cells. Moreover, although the gamma/delta cell clones lysed other target cells (e.g., Molt 4, U937, Jurkat etc.), these latter targets did not induce delta modulation or IL-2R expression. In addition, F(ab)2 anti-CD3 antibodies inhibited activated gamma/delta T cells from killing K562 but did not inhibit the lysis of the other targets. Taken together, these results suggest that gamma/delta cells lyse some targets by utilizing receptors (perhaps NK-like) distinct from the gamma/delta receptor. We also found that triggering of the gamma/delta receptor by K562 inhibited the capacity of resting gamma/delta to lyse Molt 4 cells under conditions in which the K562 cells were not lysed. These findings suggest that the gamma/delta receptor maybe directly involved in the lysis of certain targets (i.e., K562) and, importantly, may potentially regulate the function of NK-like receptors that are involved in the lysis of other targets.
Di Fabrizio
L
L
Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, NY 10032.
Kimura
Y
Y
Ware
R
R
Rogozinski
L
L
Chess
L
L
D000818:Animals; D018949:Antigens, CD1; D000943:Antigens, Differentiation / Q000276:immunology; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D004306:Dose-Response Relationship, Immunologic; D015536:Down-Regulation; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D016130:Immunophenotyping; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology*; D004915:Leukemia, Erythroblastic, Acute / Q000276:immunology*; D051379:Mice / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D014162:Transfection
D018949:Antigens, CD1; D000943:Antigens, Differentiation; D007140:Immunoglobulin Fab Fragments; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015375:Receptors, Interleukin-2