The Survival of Memory CD4+ T Cells within the Gut Lamina Propria Requires OX40 and CD30 Signals
The Survival of Memory CD4+ T Cells within the Gut Lamina Propria Requires OX40 and CD30 Signals
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DOI：
10.4049/jimmunol.0901514
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发表时间：
2009-10-15
影响因子：
4.4
通讯作者：
Lane, Peter J. L.
中科院分区：
文献类型：
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作者：
Withers, David R.;Jaensson, Elin;Lane, Peter J. L.
虽然CD 4（+）记忆T细胞存在于次级淋巴组织中，但这些细胞的主要储存库位于肠的固有层中。在这项研究中，我们证明，在缺乏通过OX 40和CD 30的信号，CD 4（+）T细胞从固有层全面耗尽。单独缺乏CD 30或OX 40可减少CD 4（+）T细胞数量，然而，在同时缺乏OX 40和CD 30的小鼠中，CD 4（+）T细胞损失大大加剧。这种CD 4 + T细胞的丢失不是由于归巢缺陷，因为CD 30 x OX 40缺陷型OTH细胞表达CCR 9和α 4 β 7的能力或运输到小肠的能力没有受损。口服免疫后，肠系膜淋巴结中野生型（WT）和CD 30 x OX 40缺陷型OTH细胞的引发也没有差异。然而，口服免疫后，CD 30 x OX 40缺陷型OTH细胞运输到固有层，但与WT OTH细胞相比未能持续存在。这不是由于Bcl-2或Bcl-XL的水平降低，因为这些的表达在wT和双敲除OTH细胞之间是相当的。总之，这些数据表明，通过CD 30和OX 40的信号是CD 4（+）T细胞在小肠固有层内存活所必需的。免疫学杂志，2009，183：5079-5084.
Although CD4(+) memory T cells reside within secondary lymphoid tissue, the major reservoir of these cells is in the lamina propria of the intestine. In this study, we demonstrate that, in the absence of signals through both OX40 and CD30, CD4(+) T cells are comprehensively depleted from the lamina propria. Deficiency in either CD30 or OX40 alone reduced CD4(+) T cell numbers, however, in mice deficient in both OX40 and CD30, CD4(+) T cell loss was greatly exacerbated. This loss of CD4(+) T cells was not due to a homing defect because CD30 x OX40-deficient OTH cells were not impaired in their ability to express CCR9 and alpha(4)beta(7) or traffic to the small intestine. There was also no difference in the priming of wild-type (WT) and CD30 x OX40-deficient OTH cells in the mesenteric lymph node after oral immunization. However, following oral immunization, CD30 x OX40-deficient OTH cells trafficked to the lamina propria but failed to persist compared with WT OTH cells. This was not due to reduced levels of Bcl-2 or Bcl-XL, because expression of these was comparable between wT and double knockout OTH cells. Collectively, these data demonstrate that signals through CD30 and OX40 are required for the survival of CD4(+) T cells within the small intestine lamina propria. The Journal of Immunology, 2009, 183: 5079-5084.