Kretschmer Birte, Lüthje Katja, Ehrlich Svenja, Osterloh Anke, Piedavent Melanie, Fleischer Bernhard, Breloer Minka
Bernhard-Nocht-Institute for Tropical Medicine, Bernhard-Nocht-Strasse 74, D-20359 Hamburg, Germany.
Immunol Lett. 2008 Oct 30;120(1-2):87-95. doi: 10.1016/j.imlet.2008.07.004. Epub 2008 Aug 20.
The transmembrane glycoprotein CD83 is rapidly upregulated on murine and human DC upon maturation and therefore a costimulatory function for T cell activation has been suggested. Studies employing human APC indeed showed that CD83 expression was positively correlated to the stimulatory capacity of the APC. Murine APC that were CD83 deficient however, did not display a reduced capacity to activate T cells. To elucidate this contradiction, we thoroughly compared the stimulatory capacity of CD83-overexpressing and CD83-deficient APC. Here we show that CD83 expression levels on APC did not affect the capacity of the APC to activate CD8(+) T cells. CD83 expression levels did not significantly affect CD4(+) T cell activation in vivo, but a weak positive correlation of CD83 expression with CD4(+) T cell activation was observed in vitro under suboptimal stimulation conditions. As CD83 expression also positively correlated with MHC-II but not with MHC-I expression, this differential stimulation specifically of CD4(+) T cells could be explained by a higher density of MHC-II peptide complexes on the APC surface. Taken together, our results strongly suggest that CD83 does not deliver crucial costimulatory signals to murine T cells.
跨膜糖蛋白CD83在小鼠和人类树突状细胞(DC)成熟时会迅速上调,因此有人提出它具有促进T细胞活化的共刺激功能。用人抗原呈递细胞(APC)进行的研究确实表明,CD83的表达与APC的刺激能力呈正相关。然而,缺乏CD83的小鼠APC并没有表现出激活T细胞的能力下降。为了阐明这一矛盾,我们全面比较了过表达CD83和缺乏CD83的APC的刺激能力。我们在此表明,APC上的CD83表达水平并不影响APC激活CD8⁺T细胞的能力。CD83表达水平在体内对CD4⁺T细胞活化没有显著影响,但在体外次优刺激条件下,观察到CD83表达与CD4⁺T细胞活化呈弱正相关。由于CD83表达也与MHC-II呈正相关,但与MHC-I表达无关,APC表面MHC-II肽复合物密度较高可以解释这种对CD4⁺T细胞的特异性差异刺激。综上所述,我们的结果强烈表明,CD83不会向小鼠T细胞传递关键的共刺激信号。