DOCK8 is essential for T-cell survival and the maintenance of CD8+ T-cell memory.
DOCK8 is essential for T-cell survival and the maintenance of CD8+ T-cell memory.
复制标题
DOI：
10.1002/eji.201141759
复制
发表时间：
2011-12
影响因子：
5.4
通讯作者：
Cornall, Richard J.
中科院分区：
文献类型：
--
作者：
Lambe, Teresa;Crawford, Greg;Johnson, Andy L.;Crockford, Tanya L.;Bouriez-Jones, Tiphaine;Smyth, Aisling M.;Pham, Trung H. M.;Zhang, Qian;Freeman, Alexandra F.;Cyster, Jason G.;Su, Helen C.;Cornall, Richard J.
鸟嘌呤核苷酸交换因子DOCK 8的缺乏导致与复发性鼻窦炎和病毒感染相关的人类免疫缺陷综合征。我们最近发现了一种DOCK 8缺陷型小鼠品系，该品系携带乙基亚硝基脲诱导的剪接位点突变，该突变显示由于生发中心B细胞的丧失而导致体液免疫应答不成熟。在这项研究中，我们转向T细胞免疫，以进一步研究人类免疫缺陷综合征及其与外周血CD4+和CD8+ T细胞减少的关系。DOCK 8缺陷小鼠的表征显示T细胞淋巴细胞减少症，T细胞更新增加和存活率降低。随着这些细胞向趋化因子CXCL12迁移的增加，成熟的CD4+胸腺细胞的出口减少。然而，尽管外周幼稚T细胞减少了两倍，但DOCK 8缺陷小鼠产生了正常的初级CD8+免疫应答，并且能够在急性流感病毒感染中存活。DOCK 8的限制作用在于感染后CD8+记忆T细胞的正常存活。这些发现有助于解释为什么DOCK8缺陷患者易受复发性感染的影响，并为T细胞记忆如何维持提供了新的见解。
Deficiency in the guanine nucleotide exchange factor DOCK8 causes a human immunodeficiency syndrome associated with recurrent sinopulmonary and viral infections. We have recently identified a DOCK8-deficient mouse strain, carrying an ethylnitrosourea-induced splice-site mutation that shows a failure to mature a humoral immune response due to the loss of germinal centre B cells. In this study we turned to T-cell immunity to investigate further the human immunodeficiency syndrome and its association with decreased peripheral CD4+ and CD8+ T cells. Characterisation of the DOCK8-deficient mouse revealed T-cell lymphopenia, with increased T-cell turnover and decreased survival. Egress of mature CD4+ thymocytes was reduced with increased migration of these cells to the chemokine CXCL12. However, despite the two-fold reduction in peripheral naïve T cells, the DOCK8-deficient mice generated a normal primary CD8+ immune response and were able to survive acute influenza virus infection. The limiting effect of DOCK8 was in the normal survival of CD8+ memory T cells after infection. These findings help to explain why DOCK8-deficient patients are susceptible to recurrent infections and provide new insights into how T-cell memory is sustained.
登录
查看更多内容
影响因子：
12.3
作者：
Kurisu S;Takenawa T
通讯作者：
Takenawa T
影响因子：
30.5
作者：
Kaech, SM;Tan, JT;Ahmed, R
通讯作者：
Ahmed, R
影响因子：
20.3
作者：
Meyer-Bahlburg A;Becker-Herman S;Humblet-Baron S;Khim S;Weber M;Bouma G;Thrasher AJ;Batista FD;Rawlings DJ
通讯作者：
Rawlings DJ
影响因子：
4.4
作者：
Obar, Joshua J.;Lefrancois, Leo
通讯作者：
Lefrancois, Leo
DOI：
10.1073/pnas.0806289106
发表时间：
2008-12-23
影响因子：
11.1
作者：
Leignadier, Julie;Hardy, Marie-Pierre;Labrecque, Nathalie
通讯作者：
Labrecque, Nathalie