Kaneko H, Saito K, Hashimoto H, Yagita H, Okumura K, Azuma M
Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan.
Clin Exp Immunol. 1996 Nov;106(2):218-29. doi: 10.1046/j.1365-2249.1996.d01-849.x.
CD28 on T cells provides a potent costimulatory signal for T cell activation. Down-regulation of CD28 on peripheral T cells has been reported in certain clinical conditions, but full studies on the mechanism and biological significance have not been performed. Our extensive phenotype analysis of peripheral blood lymphocytes (PBL) from SLE patients revealed that the absolute number of CD28+ T cells of both CD4 and CD8 phenotypes was selectively decreased, while that of CD28- T cells was maintained. CD28+ T cells from SLE patients exhibited mostly normal proliferative responses to both CD28-dependent and -independent stimulations. In contrast, CD28- T cells were hyporesponsive to anti-CD3 stimulation in both SLE and normal controls. These results implied that the selective decrease of CD28+ T cells in SLE does not result from a hyporesponsiveness of CD28+ T cells. To investigate the reason for the selective loss of CD28+ T cells, we determined the appearance of apoptotic cells in culture with or without anti-CD3 stimulation. Apoptotic cells defined by merocyanine (MC)540 were gradually increased from 12 h to 24 h. Anti-CD3-induced apoptosis of CD28+ T cells was significantly accelerated in SLE, whereas apoptosis of CD28- T cells was hardly detected in both SLE and normal controls. Comparative analysis between CD28+ and CD28- T cells on CD95 (Fas) and Bcl-2 expression, which are related to activation-induced cell death (AICD), did not show a major difference, although CTLA4, which has been demonstrated to transmit an apoptosis-inducing signal, was expressed only on CD28+ T cells. Our results suggest that CD28-mediated costimulation influences T cell susceptibility to AICD and may be involved in T cell lymphopenia in SLE.
T细胞上的CD28为T细胞活化提供强大的共刺激信号。在某些临床情况下，已报道外周T细胞上CD28表达下调，但尚未对其机制和生物学意义进行全面研究。我们对系统性红斑狼疮（SLE）患者外周血淋巴细胞（PBL）进行的广泛表型分析显示，CD4和CD8表型的CD28⁺ T细胞绝对数量选择性减少，而CD28⁻ T细胞数量保持不变。SLE患者的CD28⁺ T细胞对CD28依赖性和非依赖性刺激大多表现出正常的增殖反应。相比之下，在SLE患者和正常对照中，CD28⁻ T细胞对抗CD3刺激反应低下。这些结果表明，SLE中CD28⁺ T细胞的选择性减少并非源于CD28⁺ T细胞反应性降低。为了探究CD28⁺ T细胞选择性减少的原因，我们测定了在有或无抗CD3刺激的培养物中凋亡细胞的出现情况。用部花青（MC）540定义的凋亡细胞从12小时到24小时逐渐增加。抗CD3诱导的SLE患者CD28⁺ T细胞凋亡显著加速，而在SLE患者和正常对照中几乎未检测到CD28⁻ T细胞凋亡。对与活化诱导细胞死亡（AICD）相关的CD95（Fas）和Bcl-2表达进行的CD28⁺和CD28⁻ T细胞比较分析未显示出主要差异，尽管已证明可传递凋亡诱导信号的CTLA4仅在CD28⁺ T细胞上表达。我们的结果表明，CD28介导的共刺激影响T细胞对AICD的易感性，可能与SLE中的T细胞淋巴细胞减少有关。
