Parada N A, Center D M, Kornfeld H, Rodriguez W L, Cook J, Vallen M, Cruikshank W W
Pulmonary Center, Evans Memorial Department of Medicine, Boston University School of Medicine, MA 02118, USA.
J Immunol. 1998 Mar 1;160(5):2115-20.
IL-16, in a CD4-dependent manner, induces high affinity IL-2R (CD25) selectively on CD4+ T cells. Based on this observation, we determined the relative effects of IL-16 on IL-2Ralpha, beta, and gamma expression on CD4+ T cells and of IL-16/IL-2 cotreatment of resting human PBMC obtained from normal individuals on CD4+ T cell proliferation and cytokine production, in vitro. IL-16 increased CD4+ T cell IL-2Ralpha and beta expression, but had no effect on expression of IL-2Rgamma. 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, IL-16/IL-2-cotreated PBMC cultures were predominantly CD4+, CD25+ CD45RO T cells. Of the cytokines measured, IL-16 treatment alone was sufficient 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 conditions resulting in CD4+ T cell depletion.
白细胞介素-16（IL-16）以依赖CD4的方式，选择性地在CD4⁺T细胞上诱导高亲和力白细胞介素-2受体（CD25）。基于这一观察结果，我们在体外确定了IL-16对CD4⁺T细胞上白细胞介素-2受体α、β和γ表达的相对影响，以及IL-16/白细胞介素-2联合处理从正常个体获得的静息人外周血单个核细胞（PBMC）对CD4⁺T细胞增殖和细胞因子产生的影响。IL-16增加了CD4⁺T细胞白细胞介素-2受体α和β的表达，但对白细胞介素-2受体γ的表达没有影响。与单独使用任何一种细胞因子的反应相比，在存在IL-16和IL-2或IL-16和IL-15的情况下，胸苷摄取和CD4⁺T细胞数量的扩增有明显的协同作用。到第4周时，经IL-16/IL-2联合处理的PBMC培养物主要是CD4⁺、CD25⁺CD45RO T细胞。在所检测的细胞因子中，单独使用IL-16处理足以在2周时诱导粒细胞-巨噬细胞集落刺激因子（GM-CSF）的合成。IL-16/IL-2联合处理似乎并未诱导任何Th亚群的选择性增殖，因为在第2周和第4周时，扩增的细胞群体合成了Th1（如干扰素-γ）和Th2（如白细胞介素-5）类型的细胞因子。这些结果表明，IL-16可以使CD4⁺T细胞对IL-2产生反应，因此在导致CD4⁺T细胞耗竭的疾病或治疗情况下，可能是免疫重建的IL-2治疗的有用辅助手段。
