Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 43, Issue 1, Pages 188-193Publisher
WILEY-BLACKWELL
DOI: 10.1002/eji.201242824
Keywords
CD28; Costimulation; Induced gene deletion; Regulatory T (Treg) cells
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Funding
- Deutsche Forschungsgemeinschaft [SFB-TRs 43, SFB-TRs 52]
- Bundesministerium fur Bildung und Forschung through Competence Network Multiple Sclerosis
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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 a 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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