Wilde D B, Roberts K, Sturmhöfel K, Kikuchi G, Coligan J E, Shevach E M
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Eur J Immunol. 1992 Feb;22(2):483-9. doi: 10.1002/eji.1830220229.
A minor population of dendritic epidermal T cells (DETC) express the V gamma 1.1C gamma 4V delta 6 T cell receptor and T cell clones and hybridomas derived from this subset constitutively secrete cytokines in culture secondary to recognition of an autoantigen. Activation of these autoreactive cells requires the use of the vitronection receptor (VNR) as an accessory molecule which interacts with the Arg-Gly-Asp-Ser (RGDS) sequence of extracellular matrix (ECM) proteins. We have compared the functional properties of C gamma 4+ hybridomas derived from newborn thymocytes and from adult spleen with the DETC hybridomas/lines in terms of their ability to secrete cytokines spontaneously and for the use of the VNR as an accessory molecule. Almost all the C gamma 4+ thymocyte hybridomas secreted cytokines spontaneously and in the majority of lines the most prominent cytokine secreted was granulocyte-monocyte colony-stimulating factor. In contrast, none of the four splenic C gamma 4+ hybridomas secreted cytokines spontaneously although all were capable of cytokine production following activation via the T cell receptor. Although the thymocyte hybridomas did not grow as adherent cell lines in culture, constitutive cytokine production required engagement of the VNR by its ligand in ECM proteins. In all cases, cytokine production could be inhibited by an anti-VNR monoclonal antibody as well as by soluble RGDS. The strong correlation of functional and molecular properties between thymocyte C gamma 4+ hybridomas and C gamma 4+ DETC suggests that the C gamma 4+ DETC may be of thymic origin and that cells with potential for autoreactivity residing in the thymus at birth may populate other peripheral locations in the mouse. The data also support the concept that the VNR, and possibly other integrins, play a role as accessory elements for autoreactive cells and may be essential for the regulation of such activity.
一小部分树突状表皮T细胞（DETC）表达Vγ1.1Cγ4Vδ6 T细胞受体，源自该亚群的T细胞克隆和杂交瘤在识别自身抗原后于培养中组成性地分泌细胞因子。这些自身反应性细胞的激活需要使用玻连蛋白受体（VNR）作为辅助分子，该分子与细胞外基质（ECM）蛋白的精氨酸 - 甘氨酸 - 天冬氨酸 - 丝氨酸（RGDS）序列相互作用。我们已将源自新生胸腺细胞和成年脾脏的Cγ4 +杂交瘤与DETC杂交瘤/细胞系的功能特性在自发分泌细胞因子的能力以及使用VNR作为辅助分子方面进行了比较。几乎所有Cγ4 +胸腺细胞杂交瘤都自发分泌细胞因子，并且在大多数细胞系中，分泌最显著的细胞因子是粒细胞 - 单核细胞集落刺激因子。相比之下，四个脾脏Cγ4 +杂交瘤中没有一个自发分泌细胞因子，尽管所有这些杂交瘤在通过T细胞受体激活后都能够产生细胞因子。虽然胸腺细胞杂交瘤在培养中不能作为贴壁细胞系生长，但组成性细胞因子产生需要ECM蛋白中的配体与VNR结合。在所有情况下，细胞因子产生都可被抗VNR单克隆抗体以及可溶性RGDS抑制。胸腺细胞Cγ4 +杂交瘤与Cγ4 + DETC之间功能和分子特性的强相关性表明，Cγ4 + DETC可能起源于胸腺，并且出生时存在于胸腺中的具有自身反应性潜力的细胞可能在小鼠的其他外周部位聚集。数据还支持这样的概念，即VNR以及可能的其他整合素作为自身反应性细胞的辅助元件发挥作用，并且可能对于调节这种活性至关重要。
