Inhibition of lymphokine-activated killer cells by human pulmonary macrophages: discordance between up-regulation of the beta chain (p75) of the interleukin-2 receptor on CD56+ cells and limited response to interleukin-2.
Previous studies have demonstrated that interaction of interleukin-2 (IL-2) with the beta chain (p75) of the IL-2 receptor on CD56+ cells is necessary for the development of lymphokine-activated killer (LAK) activity and proliferation of CD56+ LAK cells in response to IL-2. Human pulmonary macrophages (PM) are potent inhibitors of LAK cells in vitro, and purified resident human lung lymphocytes show limited LAK activity in response to IL-2, suggesting that IL-2-p75 interactions may be altered locally in vivo. In the current study, human PM or anti-p75 inhibited LAK activity and proliferation of CD56+ cells in response to IL-2. This effect was produced by either live or paraformaldehyde-fixed PM, but not peripheral blood monocytes, suggesting that a membrane signal on PM was responsible for inhibition. Suppression of LAK function and proliferation in response to IL-2 occurred despite a rapid up-regulation of p75 on CD56+ cells after 24 h of incubation with PM. Greater than 70% of CD56+ cells expressed p75 after culture with either live or fixed PM, compared with 10 to 15% at 0 h or after 24 h of incubation in IL-2 alone. p75 dim and p75 bright cells increased equally, suggesting that p75 was being up-regulated on previously p75- cells rather than an overexpansion of one subset of p75+ cells. The increase in p75 expression in the presence of PM paralleled with an increase in IL-2 binding to these lymphocytes. These results suggest that PM inhibit the activation of LAK cells at a point distal to IL-2-p75 binding.
Yarbrough
W C
WC
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235-9034.
Wilkes
D S
DS
Weissler
J C
JC
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D001665:Binding Sites; D019002:CD56 Antigen; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D019002:CD56 Antigen; D007376:Interleukin-2; D015375:Receptors, Interleukin-2