SYNERGISTIC ACTIVATION OF CD4(-CELLS BY IL-16 AND IL-2() T)

IL-16, in a CD4-dependent manner, induces high affinity IL-2R (CD25) s electively on CD4(+) T cells. Based on this observation, we determined the relative effects of IL-16 on IL-2R alpha, beta, and gamma express ion on CD4(+) T cells and of IL-16/IL-2 cotreatment of resting human P BMC obtained from normal individuals on CD4(+) T cell proliferation an d cytokine production, in vitro. IL-16 increased CD4(+) T cell IL-2R a lpha and beta expression, but had no effect on expression of IL-2R gam ma. There was marked synergy of thymidine uptake and expansion of CD4( +) T cell numbers in the presence of IL-16 and IL-2 or IL-16 and IL-15 compared with the responses to any of the cytokines alone, By 4 wk, I L-16/IL-2-cotreated PBMC cultures were predominantly CD4(+), CD25(+) C D45RO T cells. Of the cytokines measured, IL-16 treatment alone was su fficient to induce synthesis of granulocyte-macrophage CSF by 2 wk, IL -16/IL-2 cotreatment did not appear to induce selective proliferation of any Th subset, as cytokines of both Th1 (e.g., IFN-gamma) and Th2 ( e.g., IL-5) types were synthesized by the expanded cell populations at 2 and 4 wk. These results suggest that IL-16 can prime CD4(+) T cells for IL-2 responsiveness, and therefore may be a useful adjunct to IL- 2 therapy for immune reconstitution in disease or therapeutic conditio ns resulting in CD4(+) T cell depletion.