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Cell‐intrinsic and ‐extrinsic control of T reg‐cell homeostasis and function revealed by induced CD 28 deletion

2012; Wiley; Volume: 43; Issue: 1 Linguagem: Inglês

10.1002/eji.201242824

1521-4141

Tea Gogishvili, Fred Lühder, Sandra Goebbels, Sandra Beer‐Hammer, Klaus Pfeffer, Thomas Hünig,

Immunotherapy and Immune Responses

While the requirement for CD 28 and its ligands for the generation and function of “natural” (n) T reg cells is well established, it has not been possible yet to investigate cell‐intrinsic effects after interrupted CD 28 expression. Here, we demonstrate a selective loss of T reg cells after disruption of the CD28 gene. The decline in T reg‐cell number was accompanied by reduced homeostatic proliferation, probably due to lack of costimulation during self‐antigen recognition, and by impaired T reg‐cell function including downregulation of CTLA ‐4. The decline in T reg‐cell number was unaffected by thymectomy or by the presence of CD 28 expressing T cells within the same animal, indicating that impairment of peripheral homeostasis and function of n T reg cells by CD28 deletion is cell‐intrinsic. In contrast, downregulation of CD 25, the α chain of the IL ‐2 R , did not occur in the presence of WT T cells, indicating that its expression does not depend on CD 28 signals in cis .