Functional capacity of Mycobacterium tuberculosis-specific T cell responses in humans is associated with mycobacterial load.
Functional capacity of Mycobacterium tuberculosis-specific T cell responses in humans is associated with mycobacterial load.
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DOI：
10.4049/jimmunol.1101122
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发表时间：
2011-09-01
期刊：
影响因子：
--
通讯作者：
Hanekom WA
中科院分区：
文献类型：
--
作者：
Day CL;Abrahams DA;Lerumo L;Janse van Rensburg E;Stone L;O'rie T;Pienaar B;de Kock M;Kaplan G;Mahomed H;Dheda K;Hanekom WA
慢性病毒感染中的高抗原负荷与抗原特异性 T 细胞反应受损有关；然而，慢性结核分枝杆菌 (Mtb) 感染中的抗原载量与人类 Mtb 特异性 T 细胞的功能能力之间的关系尚不清楚。我们比较了分枝杆菌负荷逐渐升高的成人（即潜伏性结核分枝杆菌感染（LTBI）、涂片-肺结核（TB）和涂片+结核患者）外周血中结核分枝杆菌特异性T细胞相关细胞因子的产生和增殖能力。与涂片-结核病和LTBI相比，涂片+结核病患者的多功能IFN-γ+IL-2+TNF-α+和产生IL-2的特异性CD4 T细胞减少，TNF-α-单阳性细胞增加。与 LTBI 相比，结核病患者的 Mtb 特异性 CD8 T 细胞频率也有所增加。 Mtb 特异性 CD4 和 CD8 T 细胞增殖能力在涂片+ TB 个体中严重受损，并与离体 IFN-γ+IL-2+TNF-α+ CD4 T 细胞呈正相关，与 TNF-α 单阳性 CD4 T 细胞呈负相关。在6个月的抗结核治疗期间，特异性IFN-γ+IL-2+TNF-α+ CD4和CD8 T细胞增加，而TNF-α-和IFN-γ-单阳性T细胞减少。这些结果表明，随着分枝杆菌负荷的增加，结核分枝杆菌特异性 T 细胞反应逐渐受损，并在治疗期间恢复反应。此外，这些数据提供了特定细胞因子产生亚群与 Mtb 特异性 T 细胞功能能力之间的联系，以及离体特定 CD8 T 细胞的存在与活动性结核病之间的联系。总而言之，这些数据对于结核病的诊断和识别结核病进展的 T 细胞相关性具有潜在的重要应用。
High antigen load in chronic viral infections has been associated with impairment of antigen-specific T cell responses; however, the relationship between antigen load in chronic Mycobacterium tuberculosis (Mtb) infection and functional capacity of Mtb-specific T cells in humans is not clear. We compared Mtb-specific T cell-associated cytokine production and proliferative capacity in peripheral blood from adults with progressively higher mycobacterial loads, i.e., persons with latent Mtb infection (LTBI), with smear − pulmonary tuberculosis (TB), and with smear+ TB. Patients with smear+ TB had decreased polyfunctional IFN-γ+IL-2+TNF-α+ and IL-2-producing specific CD4 T cells and increased TNF-α-single positive cells, when compared with smear − TB and LTBI. TB patients also had increased frequencies of Mtb-specific CD8 T cells, compared with LTBI. Mtb-specific CD4 and CD8 T cell proliferative capacity was profoundly impaired in individuals with smear+ TB, and correlated positively with ex vivo IFN-γ+IL-2+TNF-α+ CD4 T cells, and inversely with TNF-α single-positive CD4 T cells. During 6 months of anti-TB treatment, specific IFN-γ+IL-2+TNF-α+ CD4 and CD8 T cells increased, whereas TNF-α- and IFN-γ-single positive T cells decreased. These results suggest progressive impairment of Mtb-specific T cell responses with increasing mycobacterial load, and recovery of responses during therapy. Furthermore, these data provide a link between specific cytokine-producing subsets and functional capacity of Mtb-specific T cells, and between the presence of specific CD8 T cells ex vivo and active TB disease. Taken together, these data have potentially significant applications for diagnosis of TB and for identification of T cell correlates of TB disease progression.
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影响因子：
82.9
作者：
Harari A;Rozot V;Bellutti Enders F;Perreau M;Stalder JM;Nicod LP;Cavassini M;Calandra T;Blanchet CL;Jaton K;Faouzi M;Day CL;Hanekom WA;Bart PA;Pantaleo G
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作者：
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作者：
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Wherry, E. John