Jago C B, Yates J, Câmara N Olsen Saraiva, Lechler R I, Lombardi G
Department of Immunology, Imperial College London, London, UK.
Clin Exp Immunol. 2004 Jun;136(3):463-71. doi: 10.1111/j.1365-2249.2004.02478.x.
CTLA-4 (CD152), the CD28 homologue, is a costimulatory molecule with negative effects on T cell activation. In addition to its role in the termination of activation, CTLA-4 has been implicated in anergy induction and the function of regulatory cells. As an intracellular molecule, it must first relocate to the cell surface and be ligated, in order to inhibit activation. Although some studies have investigated CTLA-4 expression on CD4(+) T cells, evidence is lacking regarding the kinetics of expression, and expression on T cell subpopulations. We have investigated CTLA-4 kinetics on human purified peripheral CD4(+), naïve, memory, CD4(+)CD25(-), CD4(+)CD25(+) regulatory T cells, and T cell clones. Intracellular stores of CTLA-4 were shown to be very low in naïve T cells, whilst significant amounts were present in memory T cells and T cell clones. Cell surface CTLA-4 expression was then investigated on CD4(+)CD45RA(+) (naïve), CD4(+)CD45RO(+) (memory), CD4(+)CD25(-), and CD4(+)CD25(+) T cells. CD25 and CD45RO are both expressed by regulatory T cells. On naïve and CD4(+)CD25(-) T cells, CTLA-4 expression declined after four hours. In contrast, on memory and CD4(+)CD25(+) T cells, high levels of expression were maintained until at least 48 hours. In addition, significant CTLA-4 expression was observed on T cell clones following anergy induction, indicating the potential involvement of CTLA-4 also in this form of tolerance.
CTLA-4（CD152）是CD28的同源物，是一种对T细胞活化具有负性作用的共刺激分子。除了在活化终止中发挥作用外，CTLA-4还与无反应性诱导和调节性细胞的功能有关。作为一种细胞内分子，它必须首先重新定位到细胞表面并被连接，以便抑制活化。尽管一些研究已经调查了CD4(+) T细胞上CTLA-4的表达，但关于表达动力学以及T细胞亚群上的表达情况仍缺乏证据。我们研究了人纯化外周血CD4(+)、初始、记忆、CD4(+)CD25(-)、CD4(+)CD25(+)调节性T细胞以及T细胞克隆上CTLA-4的动力学。结果显示，初始T细胞中CTLA-4的细胞内储存量非常低，而记忆T细胞和T细胞克隆中存在大量CTLA-4。随后我们研究了CD4(+)CD45RA(+)（初始）、CD4(+)CD45RO(+)（记忆）、CD4(+)CD25(-)和CD4(+)CD25(+) T细胞上的细胞表面CTLA-4表达。CD25和CD45RO均由调节性T细胞表达。在初始和CD4(+)CD25(-) T细胞上，4小时后CTLA-4表达下降。相比之下，在记忆和CD4(+)CD25(+) T细胞上，高水平表达至少维持到48小时。此外，在无反应性诱导后的T细胞克隆上观察到显著的CTLA-4表达，表明CTLA-4也可能参与这种形式的耐受性。
