TNF alpha enhancement of NK and LAK cell functions induced by high-dose IL-2 in human peripheral blood mononuclear cells from patients pretreated with alpha IFN + IL-2.

In this study we analyzed the induction of NK and LAK cell functions by TNF alpha, alone or combined with IL-2, in 4 days in vitro culture of PBMC from patients treated with alpha IFN + IL-2. Although the MN cell recovery after 4 days culture was very similar with TNF alpha alone or with IL-2 alone, TNF alpha did not maintain nor induce LAK or NK activities of in vivo preactivated PBMC. When compared to preculture values, TNF alpha alone induced a preferential outgrowth of CD4+ T cells together with a decrease of CD8+ T cells, NK cells and IL-2R (p55)-expressing cells. The combination of TNF alpha (100 ng) and high dose IL-2 (9,000 IUg/ml) did not improve the MN cell recovery after 4 days culture; but increased IL-2-induced NK activities in PBMC from 6/7 patients, and IL-2-induced LAK activities in 4/7 patients. However, these variations were not significant. The combination of TNF alpha and lower doses of IL-2, ranging from 150 IU/ml to 30 IU/ml, did not modify MN cell recovery in culture nor IL-2-induced NK and LAK cell activities. When compared to paired samples cultured with IL-2 alone, the combination of TNF alpha with all doses of IL-2 did not modify the distribution of T and NK cells, but increased the expression of CD8 on NK cells. Furthermore, the combination of TNF alpha and IL-2 increased the expression of IL-2R (p55) on PBMC but the expression of this receptor was restricted to CD4+ T cells and did not appear on NK cells.