PD-1 deficiency promotes TFH cells expansion in ITV-immunized mice by upregulating cytokines secretion.
PD-1 deficiency promotes TFH cells expansion in ITV-immunized mice by upregulating cytokines secretion.
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PD-1缺陷通过上调细胞因子分泌促进ITV免疫小鼠中TFH细胞的扩增
DOI：
10.1186/s13071-018-2984-4
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发表时间：
2018-07-06
影响因子：
3.2
通讯作者：
Xu W
中科院分区：
文献类型：
--
作者：
Liu T;Cheng X;Ding Y;Zhu F;Fu Y;Peng X;Xu W
研究背景滤泡辅助性T细胞（TFH）是体液免疫的基础。我们在前期的研究中发现PD-1缺陷能显著促进疟原虫特异性TFH细胞的扩增，增强ITV（infection treatment vaccine）免疫小鼠的体液免疫。然而，PD-1信号调节TFH细胞活化的潜在机制仍不清楚。流式细胞仪检测CD 11 c + CXCR 5+树突状细胞（DCs）的活化表型、脾滤泡调节性T细胞（TFR细胞）、疟原虫特异性TFH细胞和生殖中心（GC）B细胞的频率和数量。血清细胞因子的水平进行了定量使用流式细胞仪珠阵列（CBA）和体内细胞因子中和进行了根据先前描述的协议和验证血清cytokine detecting.ResultsWe发现，PD-1-/-naïve和免疫小鼠有更多的TFR细胞在脾脏比WT和WT免疫小鼠。此外，引发TFH细胞的CXCR 5 +DC在ITV免疫的WT和PD-1-/-小鼠中以相似水平活化。然而，在ITV免疫的PD-1-/-小鼠中，IL-10、IFN-γ和MCP-1的血清水平显著增加，并且用抗IL-10、抗IFN-γ或抗MCP-1中和抗体在体内处理显著损害TFH细胞和GC B细胞的发育。IFN-γ和MCP-1。这些结果有助于设计一种有效的疟疾疫苗，目的是诱导体液免疫反应。
BackgroundT follicular helper (TFH) cells are fundamental for the development of humoral immunity. In our previous study, we found that PD-1 deficiency substantially promoted the expansion ofPlasmodium-specific TFH cells and enhanced the humoral immunity of ITV (infection treatment vaccine)-immunized mice. However, the underlying mechanism by which PD-1 signaling modulates TFH cells activation remains unclear.MethodsMice were immunized with the ITV following the standard procedures. The activation phenotype of CD11c+CXCR5+dendritic cells (DCs), the frequency and number of splenic follicular regulatory T cells (TFR cells),Plasmodium-specific TFH cells and germinal center (GC) B cells were analyzed by FACS. The levels of serum cytokines were quantified using the cytometric bead array (CBA) andin vivocytokine neutralization was carried out according to a previously described protocol and verified by serum cytokine detection.ResultsWe found that PD-1-/-naïve and immunized mice had more TFR cells in the spleen than WT and WT immunized mice. Additionally, CXCR5+DC, which prime TFH cells, were activated at similar levels in ITV-immunized WT and PD-1-/-mice. However, the serum levels of IL-10, IFN-γ and MCP-1 were significantly increased in ITV-immunized PD-1-/-mice, and treatment with an anti-IL-10, anti-IFN-γ or anti-MCP-1 neutralizing antibodyin vivomarkedly impaired the development of TFH cells and GC B cells.ConclusionsOur findings demonstrate that the modulation of TFH cells by PD-1 signaling is dependent on the cytokines IL-10, IFN-γ and MCP-1 in ITV-immunized mice. These results could facilitate the design of an effective malaria vaccine with the aim of inducing humoral immune responses.
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影响因子：
30.5
作者：
Butler, Noah S.;Moebius, Jacqueline;Pewe, Lecia L.;Traore, Boubacar;Doumbo, Ogobara K.;Tygrett, Lorraine T.;Waldschmidt, Thomas J.;Crompton, Peter D.;Harty, John T.
通讯作者：
Harty, John T.
影响因子：
5.4
作者：
Long CA;Zavala F
通讯作者：
Zavala F
影响因子：
3.7
作者：
Mancini F;Monaci E;Lofano G;Torre A;Bacconi M;Tavarini S;Sammicheli C;Arcidiacono L;Galletti B;Laera D;Pallaoro M;Tuscano G;Fontana MR;Bensi G;Grandi G;Rossi-Paccani S;Nuti S;Rappuoli R;De Gregorio E;Bagnoli F;Soldaini E;Bertholet S
通讯作者：
Bertholet S
DOI：
10.1073/pnas.1112648109
发表时间：
2012-01-24
影响因子：
11.1
作者：
Moon, James J.;Suh, Heikyung;Irvine, Darrell J.
通讯作者：
Irvine, Darrell J.
影响因子：
4.4
作者：
Liu, Taiping;Xu, Guilian;Xu, Wenyue
通讯作者：
Xu, Wenyue