Hougardy Jean-Michel, Place Sammy, Hildebrand Marc, Drowart Annie, Debrie Anne-Sophie, Locht Camille, Mascart Francoise
Laboratory of Vaccinology and Mucosal Immunity, Hôpital Erasme, Brussels, Belgium.
Am J Respir Crit Care Med. 2007 Aug 15;176(4):409-16. doi: 10.1164/rccm.200701-084OC. Epub 2007 May 31.
Tuberculosis (TB) remains a leading cause of death, and the role of T-cell responses to control Mycobacterium tuberculosis infections is well recognized. Patients with latent TB infection develop strong IFN-gamma responses to the protective antigen heparin-binding hemagglutinin (HBHA), whereas patients with active TB do not.
We investigated the mechanism of this difference and evaluated the possible involvement of regulatory T (Treg) cells and/or cytokines in the low HBHA T-cell responses of patients with active TB.
The impact of anti-transforming growth factor (TGF)-beta and anti-IL-10 antibodies and of Treg cell depletion on the HBHA-induced IFN-gamma secretion was analyzed, and the Treg cell phenotype was characterized by flow cytometry.
Although the addition of anti-TGF-beta or anti-IL-10 antibodies had no effect on the HBHA-induced IFN-gamma secretion in patients with active TB, depletion of CD4(+)CD25(high)FOXP3(+) T lymphocytes resulted in the induction by HBHA of IFN-gamma concentrations that reached levels similar to those obtained for latent TB infection. No effect was noted on the early-secreted antigen target-6 or candidin T-cell responses.
Specific CD4(+)CD25(high)FOXP3(+) T cells depress the T-cell-mediated immune responses to the protective mycobacterial antigen HBHA during active TB in humans.
结核病仍然是主要的死亡原因之一，T细胞反应在控制结核分枝杆菌感染中的作用已得到充分认识。潜伏性结核感染患者对保护性抗原肝素结合血凝素（HBHA）产生强烈的γ干扰素反应，而活动性结核患者则不然。
我们研究了这种差异的机制，并评估了调节性T（Treg）细胞和/或细胞因子在活动性结核患者低HBHA T细胞反应中的可能作用。
分析抗转化生长因子（TGF）-β和抗白细胞介素-10抗体以及Treg细胞耗竭对HBHA诱导的γ干扰素分泌的影响，并通过流式细胞术对Treg细胞表型进行表征。
虽然添加抗TGF-β或抗白细胞介素-10抗体对活动性结核患者HBHA诱导的γ干扰素分泌没有影响，但CD4(+)CD25(高)FOXP3(+) T淋巴细胞的耗竭导致HBHA诱导的γ干扰素浓度达到与潜伏性结核感染相似的水平。对早期分泌抗原靶标-6或念珠菌素T细胞反应未观察到影响。
在人类活动性结核期间，特异性CD4(+)CD25(高)FOXP3(+) T细胞会抑制对保护性分枝杆菌抗原HBHA的T细胞介导的免疫反应。
