CD4 T follicular helper cell dynamics during SIV infection
CD4 T follicular helper cell dynamics during SIV infection
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DOI：
10.1172/jci63039
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发表时间：
2012-09-01
影响因子：
15.9
通讯作者：
Koup, Richard A.
中科院分区：
文献类型：
--
作者：
Petrovas, Constantinos;Yamamoto, Takuya;Koup, Richard A.
CD 4 T滤泡辅助细胞（TFH）与抗原特异性B细胞相互作用并刺激其产生。TFH细胞与B细胞的相互作用与SIV特异性免疫球蛋白的产生相关。然而，TFH细胞的命运及其参与SIV诱导的抗体产生还不清楚。我们研究了恒河猴TFH细胞的表型、功能、位置和分子特征。与人类类似，恒河猴中的TFH细胞在细胞因子功能方面代表了异质性群体。在高度分化的TFH细胞亚群中，其特征在于CD 150（lo）表达，Th 1细胞因子的产生受到损害，而IL-4的产生增加，并且细胞表现出降低的存活、循环和运输能力。TFH细胞表现出一个独特的基因谱，被SIV感染显著改变。TFH细胞被SIV感染;然而，在一些动物中，这些细胞实际上在慢性SIV感染期间积累。在SIV感染期间，全身免疫激活和IL-6产生增加有助于驱动TFH分化。TFH细胞的积累与激活的生发中心B细胞和SIV特异性抗体的频率增加有关。因此，慢性SIV不会干扰TFH细胞帮助B细胞成熟和产生SIV特异性免疫球蛋白的能力。
CD4 T follicular helper (TFH) cells interact with and stimulate the generation of antigen-specific B cells. TFH cell interaction with B cells correlates with production of SIV-specific immunoglobulins. However, the fate of TFH cells and their participation in SIV-induced antibody production is not well understood. We investigated the phenotype, function, location, and molecular signature of TFH cells in rhesus macaques. Similar to their human counterparts, TFH cells in rhesus macaques represented a heterogeneous population with respect to cytokine function. In a highly differentiated subpopulation of TFH cells, characterized by CD150(lo) expression, production of Th1 cytokines was compromised while IL-4 production was augmented, and cells exhibited decreased survival, cycling, and trafficking capacity. TFH cells exhibited a d.istinct gene profile that was markedly altered by SIV infection. TFH cells were 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 cells was associated with increased frequency of activated germinal center B cells and SIV-specific antibodies. Therefore, chronic SIV does not disturb the ability of TFH cells to help B cell maturation and production of SIV-specific immunoglobulins.