Impairment of CD8+ T suppressor cell function in patients with active systemic lupus erythematosus
Impairment of CD8+ T suppressor cell function in patients with active systemic lupus erythematosus
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DOI：
10.4049/jimmunol.166.10.6452
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发表时间：
2001-05-15
影响因子：
4.4
通讯作者：
Indiveri, F
中科院分区：
文献类型：
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作者：
Filaci, G;Bacilieri, S;Indiveri, F
系统性红斑狼疮(SLE)患者存在T细胞抑制功能的改变。最近，通过将纯化的CD8(+)T细胞与IL-2和GM-CSF孵育，在体外产生了CD8(+)T抑制淋巴细胞(CD8+ts)。使用这种方法，我们从受SLE影响的患者中产生了CD8(+)T细胞。SLE患者CD8(+)ts表型与正常人无显著差异。活动期SLE患者的CD8(+)T细胞对抗CD3单抗诱导的自体PBMC增殖无明显抑制作用，而缓解期SLE患者的CD8(+)T细胞具有与正常人相当的抑制活性。CD8(+)TS细胞的抑制作用既不是通过细胞毒作用介导的，也不是通过诱导细胞凋亡来实现的。两种细胞因子，干扰素-γ和白介素6，被发现与CD8(+)T细胞的功能有关。事实上，CD8(+)ts抑制活性的抵消是通过用特定的抗体阻断干扰素-γ或通过反义寡核苷酸抑制CD8(+)ts介导的IL-6的分泌来实现的。有趣的是，SLE患者的CD8(+)T细胞表现出一种特殊的细胞因子模式，其特征是IL-6的分泌受损和IL-12的分泌增加。因此，抑制性(IL-6)和刺激性(IL-12)细胞因子之间平衡的改变可能是SLE患者CD8(+)T细胞功能受损的原因。
Alteration of T cell suppression function has been recognized in patients with systemic lupus erythematosus (SLE). Recently, CD8(+) T suppressor lymphocytes (CD8+ Ts) have been generated in vitro by incubating purified CD8(+) T cells with IL-2 and GM-CSF. Using this method, we generated CD8(+) Ts from patients affected by SLE. No major differences were found in the CD8(+) Ts phenotype between SLE patients and healthy subjects. CD8(+) Ts from SLE patients with active disease did not inhibit the anti-CD3 mAb-induced proliferation of autologous PBMC, whereas CD8(+) Ts from SLE patients in remission exerted an inhibitory activity comparable to normal subjects. The inhibitory effect of CD8(+) Ts cells was neither mediated by cytotoxic activity nor by apoptosis induction. Two cytokines, IFN-gamma and IL-6, were found to be responsible for the function of CD8(+) Ts. In fact, counteraction of CD8(+) Ts suppression activity was obtained by blocking IFN-gamma with a specific Ab or by inhibiting CD8(+) Ts-mediated IL-6 secretion by an antisense oligonucleotide. Interestingly, CD8(+) Ts from SLE patients showed a peculiar cytokine pattern characterized by an impaired secretion of IL-6 and an increased secretion of IL-12. Thus, it appears that an altered balance between inhibitory (IL-6) and stimulatory (IL-12) cytokines might be responsible for the functional impairment of CD8(+) Ts in SLE patients.