Gaspari A A, Jenkins M K, Katz S I
Dermatology Branch, National Cancer Institute, Bethesda, MD 20892.
J Immunol. 1988 Oct 1;141(7):2216-20.
Previous studies of Ia+ keratinocytes (KC) indicated that they functioned poorly or not at all when utilized as accessory cells for T cell activation. When Ia+ KC were modified with trinitrobenzene sulfonic acid, these cells did not induce a proliferative response in the TNP-specific, 1-Ek-restricted Th1 clone SE-4 (less than 5% of control). Analysis of supernatants generated from SE-4 cells incubated with these non-stimulatory accessory cells revealed low levels of IL-3 and IFN-gamma, but an absence of IL-2, when compared with supernatants generated from SE-4 cells stimulated with TNP-modified cultured Langerhans' cells that contain high levels of all of these lymphokines. Incubation of SE-4 cells with TNP-modified Ia+, but not Ia- KC or FITC-modified Ia+ KC, resulted in unresponsiveness to subsequent stimulation with TNP-modified functional accessory cells. Blocking studies with anti-class II MHC mAb revealed that the induction of unresponsiveness by hapten-modified Ia+ KC was restricted to the I-Ek molecule. Thus, the Ag and MHC specificities of unresponsiveness induced by TNP-modified Ia+ KC were identical to those observed for the proliferation of this clone in response to TNP-modified functional accessory cells. These data indicate the existence of a naturally occurring population of Ia+ cells that, after hapten-modification, induce an unresponsive state instead of proliferation of T cells.
先前对Ia⁺角质形成细胞（KC）的研究表明，当将它们用作T细胞活化的辅助细胞时，其功能很差或根本没有功能。当用三硝基苯磺酸修饰Ia⁺ KC时，这些细胞在TNP特异性、I-Ek限制性Th1克隆SE-4中未诱导增殖反应（不到对照的5%）。与用含有所有这些高水平淋巴因子的TNP修饰的培养朗格汉斯细胞刺激SE-4细胞产生的上清液相比，分析与这些无刺激作用的辅助细胞孵育的SE-4细胞产生的上清液发现，IL-3和IFN-γ水平较低，但没有IL-2。将SE-4细胞与TNP修饰的Ia⁺ KC（而不是Ia⁻ KC或FITC修饰的Ia⁺ KC）孵育，导致对随后用TNP修饰的功能性辅助细胞刺激无反应。用抗II类MHC单克隆抗体进行的阻断研究表明，半抗原修饰的Ia⁺ KC诱导的无反应性仅限于I-Ek分子。因此，TNP修饰的Ia⁺ KC诱导的无反应性的抗原和MHC特异性与该克隆对TNP修饰的功能性辅助细胞增殖所观察到的特异性相同。这些数据表明存在一种天然存在的Ia⁺细胞群体，在半抗原修饰后，它们诱导T细胞进入无反应状态而不是增殖。
