Baume D M, Robertson M J, Levine H, Manley T J, Schow P W, Ritz J
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115.
Eur J Immunol. 1992 Jan;22(1):1-6. doi: 10.1002/eji.1830220102.
Human natural killer (NK) cells can be subdivided into two populations based on the density of cell surface CD56 antigen. The great majority (approximately 90%) of NK cells express CD56 at low levels (the CD56dim phenotype), whereas a small NK cell subset (approximately 10%) exhibits approximately fivefold greater density of surface CD56. Exposure to exogenous interleukin 2 (IL 2) induces tenfold greater proliferation of CD56bright cells compared to CD56dim lymphocytes, even though both subsets constitutively express similar levels of intermediate affinity IL 2 receptor (IL 2R) p75 chains. Incubation with IL 2 alone or irradiated target cells alone could induce expression of the IL 2R p55 chain by both CD56bright and CD56dim NK cells; a combination of both stimuli was most effective. IL 2R p55 induction was evident after co-culture of NK cells with both NK-sensitive and NK-resistant cell lines or with antibody-coated target cells. Activation of NK cells with IL 2 plus target cells resulted in enhanced proliferation compared to activation with IL 2 alone; target cells alone did not induce significant proliferation. Although both NK cell subsets appeared to express high-affinity IL 2R p75/p55 heterodimers after stimulation with target cells and IL 2, proliferation of CD56dim cells remained minimal after such activation; activated CD56dim cells consistently demonstrated less proliferation to IL 2 than did resting CD56bright cells. In contrast, CD56bright NK cells exhibited even greater proliferation after stimulation with target cells. Almost all CD56dim NK cells expressed CD16 (Fc gamma R III) as well as the NK zeta chain, whereas less than 50% of CD56bright cells express either CD16 or zeta. CD56bright and CD56dim lymphocytes, thus, appear to represent distinct subpopulations of NK cells with different functional activities. Unlike CD56bright cells, CD56dim NK cells do not proliferate optimally to IL 2, even after the latter have been stimulated to express both IL 2R p55 and IL 2R p75. Efficient proliferation of CD56dim NK cells may, thus, require additional or alternative signals.
人类自然杀伤（NK）细胞可根据细胞表面CD56抗原的密度分为两个亚群。绝大多数（约90%）的NK细胞低水平表达CD56（CD56dim表型），而一小部分NK细胞亚群（约10%）表面CD56的密度约高五倍。与CD56dim淋巴细胞相比，暴露于外源性白细胞介素2（IL-2）可诱导CD56bright细胞增殖增加十倍，尽管两个亚群组成性表达相似水平的中等亲和力IL-2受体（IL-2R）p75链。单独用IL-2或单独用经照射的靶细胞孵育，均可诱导CD56bright和CD56dim NK细胞表达IL-2R p55链；两种刺激的组合最为有效。NK细胞与NK敏感和NK抗性细胞系或与抗体包被的靶细胞共培养后，IL-2R p55的诱导明显。与单独用IL-2激活相比，用IL-2加靶细胞激活NK细胞可导致增殖增强；单独的靶细胞不诱导显著增殖。尽管在用靶细胞和IL-2刺激后，两个NK细胞亚群似乎都表达高亲和力的IL-2R p75/p55异二聚体，但激活后CD56dim细胞的增殖仍保持在最低水平；活化的CD56dim细胞对IL-2的增殖反应始终低于静息的CD56bright细胞。相反，CD56bright NK细胞在用靶细胞刺激后表现出更强的增殖。几乎所有CD56dim NK细胞均表达CD16（FcγR III）以及NK ζ链，而不到50%的CD56bright细胞表达CD16或ζ链。因此，CD56bright和CD56dim淋巴细胞似乎代表具有不同功能活性的NK细胞不同亚群。与CD56bright细胞不同，CD56dim NK细胞即使在被刺激表达IL-2R p55和IL-2R p75后，对IL-2的增殖反应也不理想。因此，CD56dim NK细胞的有效增殖可能需要额外的或替代的信号。
