Murine regulatory T cells contain hyperproliferative and death-prone subsets with differential ICOS expression.
Murine regulatory T cells contain hyperproliferative and death-prone subsets with differential ICOS expression.
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鼠调节T细胞含有具有差异ICOS表达的高增殖性和易死的子集。
DOI：
10.4049/jimmunol.1102448
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发表时间：
2012-02-15
期刊：
影响因子：
--
通讯作者：
Zhong XP
中科院分区：
文献类型：
--
作者：
Chen Y;Shen S;Gorentla BK;Gao J;Zhong XP
调节性T细胞（Treg）对自我耐受至关重要。Treg在体外受T细胞受体（TCR）刺激后表现出低增殖的无能表型，但在体内却表现出旺盛的增殖，这一直是一个谜。我们在这里报道，与传统的T细胞（Tcon）不同，小鼠Treg细胞在体外和体内都容易死亡，但具有超增殖能力。在体外培养过程中，大多数Treg在有或没有TCR刺激的情况下死亡，这与内在死亡途径的组成性激活有关。然而，一小部分Treg群体对TCR刺激更敏感，特别是弱刺激，增殖比CD4+ Tcon更强烈，并且对激活诱导的细胞死亡有抵抗力。与Tcon相比，IL-2可增强Treg的增殖，但对cd28介导的共刺激的依赖性较低。我们进一步证明，存活和增殖的Treg是ICOS阳性，而易死亡的Treg是ICOS阴性。此外，ICOS+ Treg比ICOS−Treg具有更强的抑制活性。我们的数据表明，大量死亡有助于体外Treg的无能表型，并建议调节Treg存活作为治疗自身免疫性疾病和癌症的治疗策略。
Regulatory T cells (Treg) are crucial for self-tolerance. It has been an enigma that Treg exhibit an anergic phenotype reflected by hypo-proliferation in vitro following T cell receptor (TCR) stimulation but undergo vigorous proliferation in vivo. We report here that, different from conventional T cells (Tcon), murine Treg are prone to death but hyper-proliferative in vitro and in vivo. During in vitro culture, most Treg die with or without TCR stimulation, correlated with constitutive activation of the intrinsic death pathway. However, a small portion of the Treg population is more sensitive to TCR stimulation, particularly weak stimulation, proliferates more vigorously than CD4+ Tcon, and are resistant to activation induced cell death. Treg proliferation is enhanced by IL-2 but less dependent on CD28-mediated costimulation than Tcon. We demonstrate further that the surviving and proliferative Treg are ICOS positive while the death-prone Treg are ICOS negative. Moreover, ICOS+ Treg contain much stronger suppressive activity than ICOS− Treg. Our data indicates that massive death contributes to the anergic phenotype of Treg in vitro and suggest modulating Treg survival as a therapeutic strategy for treatment of autoimmune diseases and cancer.
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DOI：
10.4049/jimmunol.181.4.2855
发表时间：
2008-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Golovina TN;Mikheeva T;Suhoski MM;Aqui NA;Tai VC;Shan X;Liu R;Balcarcel RR;Fisher N;Levine BL;Carroll RG;Warner N;Blazar BR;June CH;Riley JL
通讯作者：
Riley JL
影响因子：
4.4
作者：
Gajewska, BU;Tafuri, A;Jordana, M
通讯作者：
Jordana, M
影响因子：
15.3
作者：
Herman, AE;Freeman, GJ;Benoist, C
通讯作者：
Benoist, C
影响因子：
32.4
作者：
De Rosa, Veronica;Procaccini, Claudio;Matarese, Giuseppe
通讯作者：
Matarese, Giuseppe
影响因子：
4.4
作者：
Akbari, Omid;Stock, Philippe;DeKruyff, Rosemarie H.
通讯作者：
DeKruyff, Rosemarie H.