CD1d-dependent expansion of NKT follicular helper cells in vivo and in vitro is a product of cellular proliferation and differentiation
CD1d-dependent expansion of NKT follicular helper cells in vivo and in vitro is a product of cellular proliferation and differentiation
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DOI：
10.1093/intimm/dxv007
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发表时间：
2015-05-01
影响因子：
4.4
通讯作者：
Lang, Mark L.
中科院分区：
文献类型：
--
作者：
Rampuria, Pragya;Lang, Mark L.
α -半乳糖神经酰胺免疫后，NKTfh细胞数量增加。NKT滤泡辅助细胞（NKTfh细胞）是最近发现的cd1限制性NKT细胞的功能亚群。鉴于NKTfh细胞促进特异性抗体反应和生发中心反应的潜力，人们对确定NKTfh细胞在体内和体外增殖和/或分化的条件非常感兴趣。我们证实表达典型的半不变性V α - 14 TCR的NKTfh细胞是CXCR5(+)/ICOS+/PD-1(+)/Bcl6(+)，并且在给C57Bl/6小鼠注射cd1结合糖脂α -半乳糖神经酰胺（α - gc）后数量增加。我们发现，α - gc刺激的NKTfh细胞的增加是cd1依赖性的，因为CD1d表达减少会减弱这种作用。在体内和体外用α - gc单独或联合IL-2处理，显示NKTfh细胞的数量比总NKT细胞增加的程度更大，但在两个群体中增殖几乎相同。从过继转移的pd -1缺失细胞群中获得NKTfh表型也很明显，表明外周NKT细胞分化为NKTfh细胞。因此，α - gc刺激的cd1依赖性外周NKTfh细胞的增加是细胞增殖和分化的结果。这些发现促进了我们对cd1结合糖脂免疫后免疫反应的理解。
Increased numbers of NKTfh cells follow immunization with alpha-galactosylceramide.NKT follicular helper cells (NKTfh cells) are a recently discovered functional subset of CD1d-restricted NKT cells. Given the potential for NKTfh cells to promote specific antibody responses and germinal center reactions, there is much interest in determining the conditions under which NKTfh cells proliferate and/or differentiate in vivo and in vitro. We confirm that NKTfh cells expressing the canonical semi-invariant V alpha 14 TCR were CXCR5(+)/ICOS+/PD-1(+)/Bcl6(+) and increased in number following administration of the CD1d-binding glycolipid alpha-galactosylceramide (alpha-GC) to C57Bl/6 mice. We show that the alpha-GC-stimulated increase in NKTfh cells was CD1d-dependent since the effect was diminished by reduced CD1d expression. In vivo and in vitro treatment with alpha-GC, singly or in combination with IL-2, showed that NKTfh cells increased in number to a greater extent than total NKT cells, but proliferation was near-identical in both populations. Acquisition of the NKTfh phenotype from an adoptively transferred PD-1-depleted cell population was also evident, showing that peripheral NKT cells differentiated into NKTfh cells. Therefore, the alpha-GC-stimulated, CD1d-dependent increase in peripheral NKTfh cells is a result of cellular proliferation and differentiation. These findings advance our understanding of the immune response following immunization with CD1d-binding glycolipids.