Tfh and B cells in HIV/SIV pathogenesis and vaccination

我们研究了恒河猴卵泡CD4T辅助细胞(TFH)的表型、功能、定位和分子特征。与人类TFH相似，它们的特征是CCR7lowPD-1HighCTLA-4HighICOSHighCXCR4高表型，在细胞因子功能方面代表了一个异质性群体。在高度分化(CD150低)的TFH细胞亚群中，Th1细胞因子的产生受到影响，而IL-4的产生增加，该细胞亚群的特征也是存活、周期和运输能力降低。与非TFH细胞相比，TFH细胞表现出一种独特的基因图谱，这种基因图谱被SIV感染显著改变。TFH细胞被发现感染了SIV，但在一些动物中，这些细胞实际上是在慢性SIV感染过程中积累的。在SIV感染过程中，全身免疫激活和IL-6产生增加有助于促进TFH的分化。TFH的积累与生发中心B细胞和SIV特异性抗体的激活频率增加有关。这些过程导致SIV中的B细胞和免疫球蛋白异常，进而导致HIV感染。

We have investigated the phenotype, function, location and molecular signature of follicular CD4 T helper cells (TFH) in rhesus macaques. Similar to human TFH, they are characterized by a CCR7lowPD-1highCTLA-4highICOShighCXCR4high phenotype and represent a heterogeneous population with respect to cytokine function. Production of Th1 cytokines was compromised while IL-4 production was augmented in a highly differentiated (CD150low) subpopulation of TFH cells that was also characterized by decreased survival, cycling, and trafficking capacity. Compared to non-TFH cells, TFH cells exhibited a distinct gene profile that was significantly altered by SIV infection. TFH cells were found to be infected by SIV yet, in some animals, these cells actually accumulated during chronic SIV infection. Generalized immune activation and increased IL-6 production helped drive TFH differentiation during SIV infection. Accumulation of TFH was associated with increased frequency of activated germinal center B cells and SIV-specific antibodies. These processes contribute to B cell and immunoglobulin abnormalities in SIV, and by extension HIV, infection.