Bordoni Veronica, Bibas Michele, Viola Domenico, Sacchi Alessandra, Cimini Eleonora, Tumino Nicola, Casetti Rita, Amendola Alessandra, Ammassari Adriana, Agrati Chiara, Martini Federico
1 Cellular Immunology Laboratory, National Institute for Infectious Diseases "L. Spallanzani" I.R.C.C.S. , Rome, Italy .
2 Clinical Department, National Institute for Infectious Diseases "L. Spallanzani" I.R.C.C.S. , Rome, Italy .
AIDS Res Hum Retroviruses. 2017 Jun;33(6):590-596. doi: 10.1089/AID.2016.0195. Epub 2017 Feb 22.
The impact of HIV infection on the frequency and differentiation capability of CD34 bone marrow hematopoietic progenitor cells (BM-HPCs) is still debated, having a possible primary role in antiretroviral-induced immunoreconstitution. We investigated the influence of HIV replication or proinflammatory cytokines on lymphopoietic capability of BM-HPCs from seven viremic (VR) and five nonviremic (NVR) HIV-infected patients. We found that BM-HPCs from VR patients were unable to differentiate in vitro toward T cells, and produced proinflammatory cytokines in the absence of viral replication. In contrast, the lymphoid differentiation potential of BM-HPCs was partially restored in successfully antiretroviral therapy-treated patients. We also showed that TLR8 triggering induced BM-HPCs from healthy donors to release proinflammatory cytokines affecting T cell differentiation. These data suggest that in HIV-infected patients, the lymphopoiesis capability of BM-HPCs may be modulated by a virus-driven autocrine mechanism involving proinflammatory cytokines.
HIV感染对CD34骨髓造血祖细胞(BM-HPCs)的频率和分化能力的影响仍存在争议,其在抗逆转录病毒诱导的免疫重建中可能起主要作用。我们研究了HIV复制或促炎细胞因子对7例病毒血症(VR)和5例非病毒血症(NVR)HIV感染患者的BM-HPCs淋巴细胞生成能力的影响。我们发现,VR患者的BM-HPCs在体外无法向T细胞分化,并且在没有病毒复制的情况下会产生促炎细胞因子。相比之下,在成功接受抗逆转录病毒治疗的患者中,BM-HPCs的淋巴细胞分化潜能部分恢复。我们还表明,触发Toll样受体8(TLR8)会诱导健康供体的BM-HPCs释放影响T细胞分化的促炎细胞因子。这些数据表明,在HIV感染患者中,BM-HPCs的淋巴细胞生成能力可能受涉及促炎细胞因子的病毒驱动自分泌机制调节。