Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Ansari Nagar, New Delhi.
Clin Immunol. 2011 Nov;141(2):133-42. doi: 10.1016/j.clim.2011.06.007. Epub 2011 Jul 1.
Leprosy is a chronic human disease; primarily affecting skin, peripheral nerves, eyes, testis etc. Comprehensive-expressional-profiling of Th1-Th2-Th3 associated markers (84 genes) using qRT-PCR array, negated the previously prevailing notion, Th2 bias towards multibacillary stage of leprosy. High production TGF-β further supported the dearth of any immune response(s) in leprosy progression. Over expression of Cbl-b, could emerge as plausible reason for contributing T cell hyporesponsiveness, possibly by degradation of T cells signaling molecules. Anti-TGF-β treatments further confirm the TGF-β-dependent-Cbl-b overexpression in multibacillary patients. Diminished Cbl-b expression in CTLA-4 knockout studies using siRNA, provided other evidence towards T cell hyporesponsiveness. Further, high T cell proliferation and IL-2 production in PBMC cultures treated with anti-TGF-β and siRNA offers here a strategy to revert T cell hyporesponsiveness by downregulating Cbl-b expression in leprosy. Thus, this study negates Th2 bias and substantiates molecular cross-talk amongst TGF-β-CTLA-4-Cbl-b eventually leads to M. leprae persistence.
麻风病是一种慢性人类疾病，主要影响皮肤、外周神经、眼睛、睾丸等。使用 qRT-PCR 阵列对 Th1-Th2-Th3 相关标志物（84 个基因）进行综合表达谱分析，否定了以前普遍存在的观点，即 Th2 偏向麻风病的多菌型阶段。高水平的 TGF-β进一步支持了麻风病进展中缺乏任何免疫反应。Cbl-b 的过度表达可能是导致 T 细胞低反应性的合理原因，可能是通过降解 T 细胞信号分子。抗 TGF-β 治疗进一步证实了 TGF-β 依赖性 Cbl-b 在多菌型患者中的过度表达。使用 siRNA 在 CTLA-4 敲除研究中减少 Cbl-b 的表达，为 T 细胞低反应性提供了其他证据。此外，用抗 TGF-β 和 siRNA 处理 PBMC 培养物可引起 T 细胞增殖和 IL-2 产生增加，这为通过下调麻风病中 Cbl-b 的表达来逆转 T 细胞低反应性提供了一种策略。因此，这项研究否定了 Th2 偏向，并证实了 TGF-β-CTLA-4-Cbl-b 之间的分子相互作用最终导致麻风分枝杆菌的持续存在。
