Dang N H, Torimoto Y, Shimamura K, Tanaka T, Daley J F, Schlossman S F, Morimoto C
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115.
J Immunol. 1991 Nov 1;147(9):2825-32.
We have recently shown that solid-phase immobilization of anti-1F7 recognizing the 110-kDa CD26 Ag is comitogenic for human peripheral blood T cell activation via both the CD3 and CD2 pathways. We have also demonstrated that binding of anti-1F7 leads to the disappearance of CD26 surface expression, and this anti-1F7-induced modulation results in an increase in anti-CD3 or anti-CD2-mediated peripheral blood T cell activation. In this report, we extended these findings by examining the expression and functional relationship of 1F7 on the CD3 and CD2 pathways of activation of human thymocytes. We now demonstrated that most of the anti-1F7 reactivity is found on medullary thymocytes, the population of thymocytes expressing high level of CD3 (CD3H). We have also shown that binding of anti-1F7 can induce a decrease in CD26 surface expression, with no detectable effect on the surface expression of CD3 or CD2. Most importantly, we showed that solid-phase immobilization of anti-1F7 has a comitogenic effect on thymocyte activation induced by anti-CD3 but not anti-CD2. In addition, anti-1F7-induced modulation of CD26 results in an enhancement in CD3-mediated but not CD2-mediated human thymocyte activation. The observed functional effect of CD26 on the CD3/TCR pathway of activation is mainly restricted to mature thymocytes as distinguished by high surface expression of CD5, although CD26 is also functionally associated with the CD3/TCR pathway on cells expressing low level of CD5. Demonstrating that CD26 involvement in the regulation of human thymocyte activation is restricted mainly to the CD3 pathway, unlike its involvement with both the CD3 and CD2 pathways of mature peripheral blood T lymphocyte activation, our data hence suggested that CD26 may play a role in thymic differentiation and maturation via the differential engagement of the CD3 pathway.
我们最近发现,识别110-kDa CD26抗原的抗1F7的固相固定通过CD3和CD2途径对人外周血T细胞活化具有协同刺激作用。我们还证明,抗1F7的结合导致CD26表面表达消失,并且这种抗1F7诱导的调节导致抗CD3或抗CD2介导的外周血T细胞活化增加。在本报告中,我们通过研究1F7在人胸腺细胞活化的CD3和CD2途径上的表达及功能关系扩展了这些发现。我们现在证明,大多数抗1F7反应性存在于髓质胸腺细胞上,即表达高水平CD3(CD3H)的胸腺细胞群体。我们还表明,抗1F7的结合可诱导CD26表面表达降低,而对CD3或CD2的表面表达无明显影响。最重要的是,我们表明抗1F7的固相固定对抗CD3诱导的胸腺细胞活化有协同刺激作用,但对抗CD2诱导的胸腺细胞活化没有协同刺激作用。此外,抗1F7诱导的CD26调节导致CD3介导的人胸腺细胞活化增强,但CD2介导的人胸腺细胞活化没有增强。CD26对活化的CD3/TCR途径的观察到的功能作用主要限于以CD5高表面表达为特征的成熟胸腺细胞,尽管CD26在表达低水平CD5的细胞上也与CD3/TCR途径功能相关。我们的数据表明,与CD26参与成熟外周血T淋巴细胞活化的CD3和CD2途径不同,CD26参与人胸腺细胞活化的调节主要限于CD3途径,因此提示CD26可能通过CD3途径的差异参与在胸腺分化和成熟中发挥作用。