INHIBITION OF T-CELL RESPONSES BY ACTIVATED HUMAN CD8+ T-CELLS IS MEDIATED BY INTERFERON-GAMMA AND IS DEFECTIVE IN CHRONIC PROGRESSIVE MULTIPLE-SCLEROSIS
INHIBITION OF T-CELL RESPONSES BY ACTIVATED HUMAN CD8+ T-CELLS IS MEDIATED BY INTERFERON-GAMMA AND IS DEFECTIVE IN CHRONIC PROGRESSIVE MULTIPLE-SCLEROSIS
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DOI：
10.1172/jci117973
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发表时间：
1995-06-01
影响因子：
15.9
通讯作者：
WEINER, HL
中科院分区：
文献类型：
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作者：
BALASHOV, KE;KHOURY, SJ;WEINER, HL
自体混合淋巴细胞反应（AMLR）涉及自体抗原呈递细胞对T细胞的激活。在AMLR过程中产生的细胞在体外具有抑制特性。在本研究中，我们研究了在AMLR中具有抑制特性的CD8 + T细胞的诱导以及这些细胞下调体外增殖反应的机制。在条件培养基中的AMLR中激活的纯化CD8 + T细胞（而非CD4 + T细胞）可抑制抗CD3或结核菌素纯蛋白衍生物（PPD）诱导的自体T细胞增殖。未激活的CD8 + T细胞无抑制作用。在条件培养基存在下于AMLR中激活的CD8 + T细胞（CD8 + Tact）为CD11b阴性且无细胞毒性。抗干扰素 - γ抗体可完全消除CD8 + Tact细胞的抑制作用，但抗白细胞介素 - 4、抗白细胞介素 - 10或抗转化生长因子 - β抗体则不能。抗白细胞介素 - 2或抗粒细胞 - 巨噬细胞集落刺激因子（GM - CSF）抗体可阻断AMLR中CD8 + Tact细胞的诱导，且这两种重组细胞因子联合可支持抑制性CD8 + Tact细胞的诱导。与复发缓解型多发性硬化症（MS）患者或正常对照相比，慢性进展型MS患者的CD8 + Tact细胞存在缺陷。我们的研究为从特定细胞因子角度理解人CD8 + T细胞的抑制机制提供了基础，并证明了这些细胞在人类自身免疫性疾病中的潜在重要性，因为其功能在进展型MS患者中存在缺陷。
The autologous mixed lymphocyte reaction (AMLR) involves the activation of T cells by autologous antigen presenting cells. Cells are generated during the course of the AMLR that have suppressive properties in vitro. In the present study we investigated the induction of CD8+ T cells in the AMLR with suppressive properties and the mechanism by which these cells downregulate in vitro proliferative responses. Purified CD8+ but not CD4+ T cells activated in the AMLR in conditioned medium inhibited proliferation of autologous T cells by anti-CD3 or PPD. Nonactivated CD8+ T cells did not suppress. The CD8+ T cells activated in the AMLR in the presence of conditioned medium (CD8+ Tact) were CD11b negative and were noncytotoxic. The inhibitory effect of CD8+ Tact cells was completely abrogated by anti-IFN-gamma antibody, but not by anti-IL-4, anti-IL-10, or anti-TGF-beta antibody. The induction of CD8+ Tact cells in the AMLR was blocked by anti-IL-2 or by anti-GM-CSF antibody and the combination of these two recombinant cytokines could support the induction of suppressive CD8+ Tact cells, CD8+ Tact cells were defective in patients with chronic progressive multiple sclerosis (MS) as compared to patients with relapsing-remitting MS or normal controls. Our studies provide a basis for understanding the mechanism of suppression by human CD8+ T cells in terms of specific cytokines, and demonstrate the potential importance of these cells in a human autoimmune disease as their function is defective in patients with progressive MS.