B cell responses to HIV antigen are a potent correlate of viremia in HIV-1 infection and improve with PD-1 blockade.
B cell responses to HIV antigen are a potent correlate of viremia in HIV-1 infection and improve with PD-1 blockade.
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DOI：
10.1371/journal.pone.0084185
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Kalams SA
中科院分区：
文献类型：
--
作者：
Nicholas KJ;Zern EK;Barnett L;Smith RM;Lorey SL;Copeland CA;Sadagopal S;Kalams SA
感染人类免疫缺陷病毒1型（HIV-1）诱导细胞和体液免疫反应的缺陷。受损的CD4+ T细胞帮助和B细胞功能障碍可能部分解释了hiv感染者中广泛中和抗体的低频率。为了了解HIV感染期间B细胞功能障碍的程度，我们评估了B细胞在基线和多种抗原刺激后的激活水平。病毒血症水平的升高与B细胞上激活标记CD86的基线表达升高有关，并且与体外灭活HIV-1刺激后B细胞增加CD86表达的能力下降有关。在一系列细胞分离实验中，自体CD4+ T细胞的存在增强了B细胞对抗原的反应。与HIV感染者相比，HIV感染者在B细胞上表达PD-1的频率更高，PD-1阻断提高了B细胞对HIV抗原的反应性，这表明HIV-1感染期间抑制分子的表达可能有助于某些观察到的B细胞缺陷。我们的研究结果表明，在慢性HIV感染期间，B细胞被激活并失去对抗原反应的全部能力，但是抑制抑制压力以及强大的CD4+ T细胞反应可能有助于保持B细胞的功能。
Infection with Human Immunodeficiency Virus Type 1 (HIV-1) induces defects of both cellular and humoral immune responses. Impaired CD4+ T cell help and B cell dysfunction may partially explain the low frequency of broadly neutralizing antibodies in HIV-infected individuals. To understand the extent of B cell dysfunction during HIV infection, we assessed the level of B cell activation at baseline and after stimulation with a variety of antigens. Increased levels of viremia were associated with higher baseline expression of the activation marker CD86 on B cells and with decreased ability of B cells to increase expression of CD86 after in vitro stimulation with inactivated HIV-1. In a series of cell isolation experiments B cell responses to antigen were enhanced in the presence of autologous CD4+ T cells. HIV infected individuals had a higher frequency of PD-1 expression on B cells compared to HIV- subjects and PD-1 blockade improved B cell responsiveness to HIV antigen, suggesting that inhibitory molecule expression during HIV-1 infection may contribute to some of the observed B cell defects. Our findings demonstrate that during chronic HIV infection, B cells are activated and lose full capacity to respond to antigen, but suppression of inhibitory pressures as well as a robust CD4+ T cell response may help preserve B cell function.
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通过PD-1-PD-1配体阻滞来振兴耗尽的HIV特异性T细胞。
影响因子：
15.3
作者：
Freeman, Gordon J.;Wherry, E. John;Ahmed, Rafi;Sharpe, Arlene H.
通讯作者：
Sharpe, Arlene H.
影响因子：
82.9
作者：
通讯作者：
--
DOI：
10.1097/qai.0b013e318224d2e9
发表时间：
2011-10-01
影响因子：
3.6
作者：
Akinsiku, Olusimidele T.;Bansal, Anju;Goepfert, Paul A.
通讯作者：
Goepfert, Paul A.
影响因子：
20.3
作者：
Klatt, Nichole R.;Vinton, Carol L.;Brenchley, Jason M.
通讯作者：
Brenchley, Jason M.
影响因子：
4.4
作者：
Malaspina, A;Moir, S;Fauci, AS
通讯作者：
Fauci, AS