Cell‐intrinsic and ‐extrinsic control of Treg‐cell homeostasis and function revealed by induced CD28 deletion. Issue 1 (17th November 2012)

• Record Type: Journal Article
• Authors: Gogishvili, Tea; Lühder, Fred; Goebbels, Sandra; Beer‐Hammer, Sandra; Pfeffer, Klaus; Hünig, Thomas
• Is Part Of: European journal of immunology. Volume 43:Issue 1(2013:Jan.)
• Page Start: 188
• Page End: 193
• Publication Date: 2012-11-17
• Subjects: Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201242824
• Languages: English
• ISSNs: 0014-2980

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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 <italic>CD28</italic> 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 <italic>CD28</italic> deletion is cell‐intrinsic. In contrast, downregulation of CD25, the α 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 <italic>cis</italic>.</p> </abstract>