Long term effect of interleukin-15 on activated natural killer cytotoxicity and CD16/56 receptor expression in HIV-infected patients

We investigated the ability of interleukin (IL)-15 to induce activated natural killer (ANK) activity and CD16/56 expression (NK cell markers) of peripheral blood mononuclear cells (MNC) from HIV-infected (HIV⁺) children and adults and normal adult controls. MNC were cultured with IL-15 for 1 to 4 weeks. ANK activity was assessed by ⁵¹Cr release assays using K562 cells. Flow cytometry assays were performed using antibodies to CD16 and CD56 receptors. The table illustrates percent lysis at an effector:target ratio of 25:1 ± standard error and mean percentage of cells ± standard error expressing both CD16 and CP56 cultured in IL-15 (10 ng/ml). K562 LYSIS (%) CD16/CD56 (%) TOTAL CD56 (%) Week Adult HIV⁺ Adult HIV⁺ Adult HIV⁺ 1** 48±7(10) 15±2(15) 5±1(8) 2±1(13) 9±1(10) 5±1(21) 1 36±6 (10)* 64±3(15)* 17±4(5)* 8±2(8)* 27±5(5)* 16±3(8)* 2 81±5(5)* 79±2(4) 18±4(5)* 11±3(7) 32±5(11)* 30±6(7) 3 69±12(6)* 40±7(5) 19±5(9)* 13±3(7) 41±7(9)* 37±3(7) 4 99±1(2)* 56±9(3) 13±5(4) 14±3(4) 45±14(4) 50±6(4) Number in parentheses = N; ** no cytokines; *P<0.05 compared to no cytokines MNC from HIV* patients were deficient compared to controls in ANK activity and in CD16/56 expression in the absence of IL-15 (week 1**). Both ANK activity and CD16/56 expression declined to <5% in patients and controls by 4 weeks without IL-15 (not shown). IL-15 enhanced ANK activity in patients and controls over 4 weeks, although there was some decline in patient response by weeks 3 and 4. IL-15 increased the percentage of NK cells (CD16⁺/56⁺) in patients and controls to comparable levels throughout the 4 week period. IL-15 also increased total CD56 expression 3-fold in patients, which may indicate expansion of a sub-population of CD16^- NK cells. In other studies, we found that IL-15 increases T suppressor cytotoxic cells (CD3⁺/8⁺) cells in HIV⁺ patients (not shown). Thus, IL-15 restores impaired ANK activity in HIV⁺ patients and may be used for immunomodulative therapy in HIV infection.