T-CELL CYTOKINE RESPONSES IN PERSONS WITH TUBERCULOSIS AND HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION
T-CELL CYTOKINE RESPONSES IN PERSONS WITH TUBERCULOSIS AND HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION
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DOI：
10.1172/jci117611
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发表时间：
1994-12-01
影响因子：
15.9
通讯作者：
BARNES, PF
中科院分区：
文献类型：
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作者：
ZHANG, M;GONG, JH;BARNES, PF
与具有免疫能力的人相比，结核病在艾滋病毒感染者中引起更广泛和更危及生命的疾病。为了调查这些严重的结核病表现可能是由于细胞因子产生的改变的假设，我们评估了HIV感染的结核病患者的细胞因子模式。在体外用结核分枝杆菌刺激后，HIV感染的结核病患者PBMC的增殖反应和1型反应减少，与HIV血清阴性的结核病患者相比，增殖反应的减少与CD4细胞计数无关，但类型1反应的减少是CD4细胞耗尽的直接结果。尽管IL-10的产生在所有结核病患者中都是显著的，但HIV感染患者的2型细胞因子的产生并没有增加。在HIV感染的结核病患者中，结核分枝杆菌诱导的增殖反应通过中和IL-10抗体而不是IL-4抗体或重组IL-12显著增强。IL-10抗体和重组IL-12均增强了结核分枝杆菌诱导的1型反应。HIV感染背景下的结核病的特点是1型反应减弱，可能是由巨噬细胞/单核细胞产生的免疫抑制细胞因子引起的，而不是由2型细胞引起的。
Tuberculosis causes more extensive and life-threatening disease in patients with HIV infection than in immunocompetent persons. To investigate the hypothesis that these severe manifestations of tuberculosis may be due to alterations in cytokine production, we evaluated cytokine patterns in HIV-infected tuberculosis patients. Upon stimulation with Mycobacterium tuberculosis in vitro, PBMC from HIV-infected tuberculosis patients had reduced proliferative and type 1 responses, compared with HIV-seronegative tuberculosis patients, The reduction in proliferative responses was independent of the CD4 cell count, but the reduced type 1 response was a direct result of CD4 cell depletion. There was no enhancement of type 2 cytokine production in HIV-infected patients, although production of IL-10 was prominent in all tuberculosis patients. In HIV-infected tuberculosis patients, M. tuberculosis-induced proliferative responses were significantly enhanced by neutralizing antibodies to IL-10 but not by antibodies to IL-4 or by recombinant IL-12. The M. tuberculosis-induced type 1 response was augmented both by antibodies to IL-10 and by recombinant IL-12. Tuberculosis in the context of HIV infection is characterized by diminished type 1 responses, probably induced by immunosuppressive cytokines produced by macrophages/monocytes, rather than by type 2 cells.