@article {542351,
	title = {Enhanced selection of FoxP3+ T-regulatory cells protects CTLA-4-deficient mice from CNS autoimmune disease.},
	journal = {Proc Natl Acad Sci U S A},
	volume = {106},
	number = {9},
	year = {2009},
	month = {2009 Mar 3},
	pages = {3306-11},
	abstract = {It is generally acknowledged that cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4/CD152) plays a pivotal role in the regulation of T-cell activation and the establishment of self-tolerance in the periphery. CTLA-4-deficient (CTLA-4KO) mice develop a lymphoproliferative disorder and die within 4 weeks of birth, suggesting a role for CTLA-4 in T-cell homeostasis or the development and activity of T-regulatory (Treg) cells. To study the role of CTLA-4 in the control of experimental autoimmune encephalomyelitis (EAE), we have generated a CTLA-4KO mouse in which >90\% of all CD4(+) T cells bear a Vbeta8.2 transgenic T-cell receptor that is specific for myelin basic protein peptide Ac1-9 (ASQKRPSQR). These mice do not develop spontaneous lymphoproliferative disease or EAE and are resistant to disease induction. This correlates with a higher frequency of functional FoxP3(+) Treg cells in the spleen and thymus of CTLA-4KO mice. The absence of CTLA-4-mediated suppression of CD28 signaling resulted in the early expression of FoxP3 on double-positive cells in the thymic cortex. We conclude that CTLA-4 is not essential for the peripheral function of FoxP3(+) Treg cells but plays a pivotal role in their thymic selection.},
	keywords = {Animals, Antigens, CD, CTLA-4 Antigen, Disease Models, Animal, Encephalomyelitis, Autoimmune, Experimental, Female, Forkhead Transcription Factors, Gene Deletion, Interleukin-2 Receptor alpha Subunit, Male, Mice, Mice, Knockout, Spleen, Thymus Gland},
	issn = {1091-6490},
	doi = {10.1073/pnas.0803186106},
	author = {Verhagen, Johan and Gabrysov{\'a}, Leona and Minaee, Sophie and Sabatos, Catherine A and Anderson, Graham and Sharpe, Arlene H and Wraith, David C}
}
