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Publication : Murine regulatory T cells contain hyperproliferative and death-prone subsets with differential ICOS expression.

First Author  Chen Y Year  2012
Journal  J Immunol Volume  188
Issue  4 Pages  1698-707
PubMed ID  22231701 Mgi Jnum  J:181206
Mgi Id  MGI:5309071 Doi  10.4049/jimmunol.1102448
Citation  Chen Y, et al. (2012) Murine regulatory T cells contain hyperproliferative and death-prone subsets with differential ICOS expression. J Immunol 188(4):1698-707
abstractText  Regulatory T cells (Treg) are crucial for self-tolerance. It has been an enigma that Treg exhibit an anergic phenotype reflected by hypoproliferation in vitro after TCR stimulation but undergo vigorous proliferation in vivo. We report in this study that murine Treg are prone to death but hyperproliferative in vitro and in vivo, which is different from conventional CD4(+)Foxp3(-) T cells (Tcon). 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 is resistant to activation-induced cell death. Treg proliferation is enhanced by IL-2 but is less dependent on CD28-mediated costimulation than that of Tcon. We demonstrate further that the surviving and proliferative Treg are ICOS(+) whereas the death-prone Treg are ICOS(-). Moreover, ICOS(+) Treg contain much stronger suppressive activity than that of ICOS(-) Treg. Our data indicate that massive death contributes to the anergic phenotype of Treg in vitro and suggest modulation of Treg survival as a therapeutic strategy for treatment of autoimmune diseases and cancer.
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