| First Author | Friedline RH | Year | 2009 |
| Journal | J Exp Med | Volume | 206 |
| Issue | 2 | Pages | 421-34 |
| PubMed ID | 19188497 | Mgi Jnum | J:146644 |
| Mgi Id | MGI:3838082 | Doi | 10.1084/jem.20081811 |
| Citation | Friedline RH, et al. (2009) CD4+ regulatory T cells require CTLA-4 for the maintenance of systemic tolerance. J Exp Med 206(2):421-34 |
| abstractText | Cytotoxic T lymphocyte antigen-4 (CTLA-4) plays a critical role in negatively regulating T cell responses and has also been implicated in the development and function of natural FOXP3(+) regulatory T cells. CTLA-4-deficient mice develop fatal, early onset lymphoproliferative disease. However, chimeric mice containing both CTLA-4-deficient and -sufficient bone marrow (BM)-derived cells do not develop disease, indicating that CTLA-4 can act in trans to maintain T cell self-tolerance. Using genetically mixed blastocyst and BM chimaeras as well as in vivo T cell transfer systems, we demonstrate that in vivo regulation of Ctla4(-/-) T cells in trans by CTLA-4-sufficient T cells is a reversible process that requires the persistent presence of FOXP3(+) regulatory T cells with a diverse TCR repertoire. Based on gene expression studies, the regulatory T cells do not appear to act directly on T cells, suggesting they may instead modulate the stimulatory activities of antigen-presenting cells. These results demonstrate that CTLA-4 is absolutely required for FOXP3(+) regulatory T cell function in vivo. |
