Opposing effects of CTLA4 insufficiency on regulatory versus conventional T cells in autoimmunity converge on effector memory in target tissue.
Opposing effects of CTLA4 insufficiency on regulatory versus conventional T cells in autoimmunity converge on effector memory in target tissue.
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自身免疫性中CTLA4不足对调节性T细胞与常规T细胞的相反影响会融合目标组织中效应的记忆。
DOI：
10.4049/jimmunol.1400876
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发表时间：
2014-11-01
期刊：
影响因子：
--
通讯作者：
Chen Z
中科院分区：
文献类型：
--
作者：
Devarajan P;Miska J;Lui JB;Swieboda D;Chen Z
Quantitative variations in CTLA4 expression, due to genetic polymorphisms, are associated with various human autoimmune conditions, including type 1 diabetes (T1D). Extensive studies have demonstrated that CTLA4 is not only essential for the suppressive role of regulatory T (Treg) cells, but also required for intrinsic control of conventional T (Tconv) cells. We report that a modest insufficiency of CTLA4 in mice, which mimics the effect of some human CTLA4 genetic polymorphisms, accompanied by a T1D-permissive MHC locus, was sufficient to induce juvenile-onset diabetes on an otherwise T1D-resistant genetic background. Reduction in CTLA4 levels had an unanticipated effect in promoting Treg cell function both in vivo and in vitro. It led to an increase in Treg memory in both lymphoid and nonlymphoid target tissue. Conversely, modulating CTLA4 by either RNAi or antibody blockade promoted effector memory (TEM) formation in the Tconv compartment. The CD4+ TEM cells, including those within target tissue, produced IL17 or IFNγ. Blocking IL7 signaling reduced the Th17 autoimmune compartment, but did not suppress the T1D induced by CTLA4 insufficiency. Enhanced effector memory formation in both Tconv and Treg lineages may underpin the apparently dichotomized impact of CTLA4 insufficiency on autoimmune pathogenesis. Therefore, while the presence of CTLA4 plays a critical role in controlling homeostasis of T cells, its quantitative variation may impose diverse or even opposing effects on distinct lineages of T cells, an optimal sum of which is necessary for preservation of T-cell immunity while suppressing tissue damage.
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影响因子：
30.5
作者：
通讯作者：
--
抗原特异性记忆调节CD4+ FOXP3+ T细胞控制对流感病毒感染的记忆反应。
DOI：
10.4049/jimmunol.1203140
发表时间：
2013-04-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Brincks EL;Roberts AD;Cookenham T;Sell S;Kohlmeier JE;Blackman MA;Woodland DL
通讯作者：
Woodland DL
影响因子：
7.7
作者：
Gerold KD;Zheng P;Rainbow DB;Zernecke A;Wicker LS;Kissler S
通讯作者：
Kissler S
DOI：
10.1084/jem.20030735
发表时间：
2003-12-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kondrack RM;Harbertson J;Tan JT;McBreen ME;Surh CD;Bradley LM
通讯作者：
Bradley LM
影响因子：
4.4
作者：
Chee, Jonathan;Ko, Hyun-Ja;Krishnamurthy, Balasubramanian
通讯作者：
Krishnamurthy, Balasubramanian