Selective expansion and partial activation of human NK cells and NK receptor-positive T cells by IL-2 and IL-15

IL-2 and IL-15 are lymphocyte growth factors produced by different cell typ es with overlapping functions in immune responses. Both cytokines costimula te lymphocyte proliferation and activation, while IL-15 additionally promot es the development and survival of NK cells, NKT cells, and intraepithelial lymphocytes. We have investigated the effects of IL-2 and IL-15 on prolife ration, cytotoxicity, and cytokine secretion by human PBMC subpopulations i n vitro. Both cytokines selectively induced the proliferation of NK cells a nd CD56(+) T cells, but not CD56(-) lymphocytes. All NK and CD56(+) T cell subpopulations tested (CD4(+), CD8(+), CD4(-)CD8(-), alpha beta TCR+, gamma delta TCR+, CD16(+), CD161(+), CD158a(+), CD158b(+), KIR3DL1(+), and CD94( +)) expanded in response to both cytokines, whereas all CD56(-) cell subpop ulations did not. Therefore, previously reported IL-15-induced gamma delta and CD8(+) T cell expansions reflect proliferations of NK and CD56(+) T cel ls that most frequently express these phenotypes. IL-15 also expanded CD8 a lpha (+)beta (-) and V alpha 24V beta 11 TCR+ T cells. Both cytokines stimu lated cytotoxicity by NK and CD56(+) T cells against K562 targets, but not the production of IFN-gamma, TNF-alpha, IL-2, or IL-4. However, they augmen ted cytokine production in response to phorbol ester stimulation or CD3 cro ss-linking by inducing the proliferation of NK cells and CD56(+) T cells th at produce these cytokines at greater frequencies than other T cells. These results indicate that IL-2 and IL-15 act at different stages of the immune response by expanding and partially activating NK receptor-positive lympho cytes, but, on their own, do not influence the Th1/Th2 balance of adaptive immune responses.