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 CD56-2( CELLS AND LIMITED RESPONSE TOINTERLEUKIN)

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) ac tivity and proliferation of CD56+ LAK cells in response to IL-2. Human pulmonary macrophages (PM) are potent inhibitors of LAK cells in vitr o, and purified resident human lung lymphocytes show limited LAK activ ity 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 in hibited LAK activity and proliferation of CD56+ cells in response to I L-2. This effect was produced by either live or paraformaldehyde-fixed PM, but not peripheral blood monocytes, suggesting that a membrane si gnal on PM was responsible for inhibition. Suppression of LAK function and proliferation in response to IL-2 occurred despite a rapid up-reg ulation of p75 on CD56+ cells after 24 h of incubation with PM. Greate r 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 incubat ion in IL-2 alone. p75 dim and p75 bright cells increased equally, sug gesting that p75 was being up-regulated on previously p75- cells rathe r than an overexpansion of one subset of p75+ cells. The increase in p 75 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.