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Publication : Cell-intrinsic and -extrinsic control of Treg-cell homeostasis and function revealed by induced CD28 deletion.

First Author  Gogishvili T Year  2013
Journal  Eur J Immunol Volume  43
Issue  1 Pages  188-93
PubMed ID  23065717 Mgi Jnum  J:191101
Mgi Id  MGI:5460951 Doi  10.1002/eji.201242824
Citation  Gogishvili T, et al. (2013) Cell-intrinsic and -extrinsic control of Treg-cell homeostasis and function revealed by induced CD28 deletion. Eur J Immunol 43(1):188-93
abstractText  While the requirement for CD28 and its ligands for the generation and function of "natural" (n)Treg cells is well established, it has not been possible yet to investigate cell-intrinsic effects after interrupted CD28 expression. Here, we demonstrate a selective loss of Treg cells after disruption of the CD28 gene. The decline in Treg-cell number was accompanied by reduced homeostatic proliferation, probably due to lack of costimulation during self-antigen recognition, and by impaired Treg-cell function including downregulation of CTLA-4. The decline in Treg-cell number was unaffected by thymectomy or by the presence of CD28 expressing T cells within the same animal, indicating that impairment of peripheral homeostasis and function of nTreg cells by CD28 deletion is cell-intrinsic. In contrast, downregulation of CD25, the alpha chain of the IL-2R, did not occur in the presence of WT T cells, indicating that its expression does not depend on CD28 signals in cis.
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