Girard Alexandre, Vergnon-Miszczycha Delphine, Depincé-Berger Anne-Emmanuelle, Roblin Xavier, Lutch Frederic, Lambert Claude, Rochereau Nicolas, Bourlet Thomas, Genin Christian, Paul Stéphane
*Groupe Immunité des Muqueuses et Agents Pathogènes, Université de Saint-Etienne, Université de Lyon; †Service de Maladies Infectieuses et Tropicales; ‡Laboratoire d'Immunologie; §Service d'Hépato-gastroentérologie; and ‖Laboratoire de Virologie, Centre Hospitalo-Universitaire Nord, Saint-Etienne, France.
J Acquir Immune Defic Syndr. 2016 Jul 1;72(3):259-65. doi: 10.1097/QAI.0000000000000943.
Correlation between GALT homing markers on lymphocytes and the low blood CD4 T-cell reconstitution in immunological nonresponders (INRs) has been studied.
Thirty-one INRs, 19 immunological responders (IRs), and 12 noninfected controls were enrolled in this study. INRs were defined by an undetectable plasma viral load RNA less than 40 copies per milliliter and CD4 T-cell count <500 cells per cubic milliliter in at least 3 years.
A complete peripheral and mucosal lymphocyte immunophenotyping was performed on these patients with a focus on the CCR9, CCR6, and α4β7 gut-homing markers.
A highly significant upregulation of α4β7 on INRs peripheral lymphocytes compared with that of IRs has been observed. This upregulation impacts different lymphocyte subsets namely CD4, CD8, and B lymphocytes. The frequency of β7 Th17 and Treg cells are increased compared with IRs and healthy controls. The frequency of β7 CD8 T cells in the blood is negatively correlated with integrated proviral DNA in rectal lymphoid cells in contrast to β7 CD4 T cells associated with HIV integration.
Alteration of lymphocyte homing abilities would have deleterious effects on GALT reconstitution and could participate to HIV reservoir constitution. These results emphasize the great interest to consider α4β7-targeted therapy in INR patients to block homing of lymphocytes and/or to directly impair gp120-α4β7 interactions.
研究淋巴细胞上的肠道相关淋巴组织（GALT）归巢标志物与免疫无反应者（INR）血液中CD4 T细胞重建不良之间的相关性。
本研究纳入了31名免疫无反应者、19名免疫反应者（IR）和12名未感染对照者。免疫无反应者定义为血浆病毒载量RNA检测不到（每毫升少于40拷贝）且CD4 T细胞计数在至少3年内<500个细胞/立方毫米。
对这些患者进行了全面的外周血和黏膜淋巴细胞免疫表型分析，重点关注CCR9、CCR6和α4β7肠道归巢标志物。
与免疫反应者相比，观察到免疫无反应者外周淋巴细胞上的α4β7显著上调。这种上调影响不同的淋巴细胞亚群，即CD4、CD8和B淋巴细胞。与免疫反应者和健康对照相比，β7 Th17和调节性T细胞（Treg）的频率增加。血液中β7 CD8 T细胞的频率与直肠淋巴样细胞中的整合前病毒DNA呈负相关，而与HIV整合相关的β7 CD4 T细胞相反。
淋巴细胞归巢能力的改变会对肠道相关淋巴组织的重建产生有害影响，并可能参与HIV储存库的形成。这些结果强调了考虑对免疫无反应者患者进行α4β7靶向治疗以阻断淋巴细胞归巢和/或直接破坏gp120-α4β7相互作用的重大意义。
