Denning S M, Kurtzberg J, Le P T, Tuck D T, Singer K H, Haynes B F
Department of Medicine, Duke University School of Medicine, Durham, NC 27710.
Proc Natl Acad Sci U S A. 1988 May;85(9):3125-9. doi: 10.1073/pnas.85.9.3125.
To study the role that epithelial cells of the thymic microenvironment play in promoting activation of immature CD7+, CD2+, CD4-, CD8- (double-negative) human thymocytes, we have isolated thymocyte subsets from normal postnatal thymus and have cocultured autologous double-negative thymocytes with pure populations of thymic epithelial (TE) cells. We report that TE cells directly activate double-negative thymocytes to proliferate and that TE cells enhance the ability of double-negative thymocytes to proliferate in response to stimulation with exogenous interleukin 2. Activated double-negative thymocytes that proliferated in vitro in the presence of TE cells and interleukin 2 remained double-negative after 23 days in culture. Moreover, TE-cell culture supernatants in the absence of intact TE cells contain interleukin 1, interleukin 3, and granulocyte/macrophage-colony-stimulating factor activity for human bone marrow cells and can activate double-negative thymocytes to proliferate. Antibodies against interleukin 1 and against granulocyte/macrophage-colony-stimulating factor inhibited TE-cell-induced thymocyte activation. These data indicate that one role of TE cells in vivo may be to activate double-negative thymocytes to proliferate.
为了研究胸腺微环境中的上皮细胞在促进未成熟的CD7⁺、CD2⁺、CD4⁻、CD8⁻（双阴性）人胸腺细胞激活过程中所起的作用，我们从出生后的正常胸腺中分离出胸腺细胞亚群，并将自体双阴性胸腺细胞与纯胸腺上皮（TE）细胞群体进行共培养。我们报告称，TE细胞可直接激活双阴性胸腺细胞使其增殖，并且TE细胞可增强双阴性胸腺细胞对外源性白细胞介素2刺激的增殖能力。在TE细胞和白细胞介素2存在的情况下于体外增殖的活化双阴性胸腺细胞在培养23天后仍保持双阴性。此外，在没有完整TE细胞的情况下，TE细胞培养上清液含有对人骨髓细胞具有活性的白细胞介素1、白细胞介素3和粒细胞/巨噬细胞集落刺激因子，并且可激活双阴性胸腺细胞增殖。针对白细胞介素1和粒细胞/巨噬细胞集落刺激因子的抗体可抑制TE细胞诱导的胸腺细胞激活。这些数据表明，TE细胞在体内的一个作用可能是激活双阴性胸腺细胞使其增殖。
