POTENTIAL ROLE FOR INTERLEUKIN-10 IN THE IMMUNOSUPPRESSION ASSOCIATED WITH KALA-AZAR
POTENTIAL ROLE FOR INTERLEUKIN-10 IN THE IMMUNOSUPPRESSION ASSOCIATED WITH KALA-AZAR
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DOI：
10.1172/jci116878
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发表时间：
1993-12-01
影响因子：
15.9
通讯作者：
LOCKSLEY, RM
中科院分区：
文献类型：
--
作者：
HOLADAY, BJ;POMPEU, MMD;LOCKSLEY, RM
急性黑热病患者在一些免疫学检测中通常是无反应的，包括T细胞增殖和体外产生巨噬细胞激活细胞因子，主要是干扰素-γ，以响应利什曼原虫抗原。为了测试潜在的免疫抑制因素，建立了一系列T细胞系和克隆，这些T细胞系和克隆来自急性黑色素瘤患者、黑色素瘤化疗后的患者以及来自同一流行地区的皮肤试验阳性的成年人。虽然从皮肤试验阳性的成人中可以很容易地建立CD4+T细胞系和克隆，但来自急性或治疗患者的系和克隆在CD8+的表达上存在严重的偏见。急性期外周血中的CD8+细胞在体外对利什曼原虫抗原本身不释放细胞因子，但对恢复1年后分离的外周血单核细胞的细胞因子谱有显著影响。CD8+细胞的加入抑制了淋巴细胞增殖和干扰素-γ的释放，促进了IL-6和IL-10的释放。CD8+细胞的抑制作用可被IL-10抗体部分阻断，但不能被IL-4抗体部分阻断。对4名急性黑色素瘤患者的分析显示，在无症状皮肤试验阳性患者的培养上清液中，IL-10的释放不能被证实。IL-10的产生可能有助于深刻抑制黑热病期间因查加西利什曼原虫而产生的干扰素-伽马的释放。
Patients with acute kala azar are generally nonreactive in a number of immunologic assays, including T cell proliferation and generation of macrophage-activating cytokines, principally IFN-gamma, in response to leishmania antigens in vitro. To test for potential immunosuppressive factors, a series of T cell lines and clones were established from patients with acute kala azar, from patients after chemotherapy for kala azar, and from skin test-positive adults from the same endemic region. Although CD4+ T cell lines and clones could be readily established from the skin test-positive adults, lines and clones from acute or treated patients were heavily biased in expression of CD8+. The CD8+ cells from acute patients did not themselves release cytokines in response to leishmania antigens in vitro, but markedly affected the cytokine profile of peripheral blood mononuclear cells isolated 1 yr later after recovery. Addition of the CD8+ cells caused inhibition of lymphoproliferation and IFN-gamma release, with augmentation of IL-6 and IL-10 release. The inhibitory effects of the CD8+ cells could be partially abrogated by antibodies to IL-10 but not by antibodies to IL-4. Analysis of four patients with acute kala azar demonstrated release of IL-10 that could not be demonstrated in supernatants from asymptomatic skin test-positive individuals. Generation of IL-10 may contribute to the profound suppression of IFN-gamma release that occurs during kala azar due to Leishmania chagasi.