Proliferation of highly purified T cells in response to signaling via surface receptors requires cell-cell contact.
Lymphocyte proliferation is associated with cell-cell aggregation. In order to assess the importance of cell-cell contact in T-cell proliferation we examined the effect of disruption of cellular aggregation by anti LFA-1(4) mAb on T-cell proliferation. Monocyte-dependent T-cell proliferation induced by anti-CD3 mAb, pairs of anti-CD2 mAbs, or PHA was inhibited by anti-LFA-1 mAb. Monocyte-independent proliferation of highly purified T cells to anti-CD3 mAb plus PMA or plus IL-2 and to PHA plus IL-2 was, surprisingly, also inhibited by anti-LFA-1 mAb. Anti-LFA-1 mAb caused the partial inhibition of both low-affinity and high-affinity IL-2 receptor and the complete inhibition of IL-2 synthesis. In contrast to the above, the proliferation of highly purified T cells to PMA plus ionomycin was not inhibited by anti-LFA-1 mAb. These results suggest that optimal activation of highly purified T cells via cell surface receptors requires LFA-1-dependent cell-to-cell contact between proliferating T cells as well as between T cells and accessory cells. Such contact appears to be crucial for initiating IL-2 production and for optimal action of IL-2 through its receptor.
Schwartz
D
D
Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115.
Wong
R C
RC
Chatila
T
T
Arnaout
A
A
Miller
R
R
Geha
R
R
D000328:Adult; D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation / Q000276:immunology*; D002449:Cell Aggregation; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins / Q000276:immunology*; D008934:Mitogens / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D008934:Mitogens; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2