title: Differential requirement for CARMA1 in agonist-selected T-cell development.
abstract: Caspase recruitment domain-containing membrane-associated guanylate kinase protein-1 (CARMA1) is a critical component of the NF-kappaB signaling cascade mediated by TCR engagement. In addition to activation of naïve T cells, TCR signaling is important for the development of agonist-selected T-cell subsets such as Treg, NKT cells, and CD8-alpha alpha T cells. However, little is known about the role of CARMA1 in the development of these lineages. Here we show that CARMA1-deficient mice (CARMA1(-/-)) have altered populations of specific subsets of agonist-selected T cells. Specifically, CARMA1(-/-) mice have impaired natural and adaptive Treg development, whereas NKT cell numbers are normal compared with wild-type mice. Interestingly, CD8-alpha alpha T cells, which may also be able to develop through an extrathymic selection pathway, are enriched in the gut of CARMA1(-/-) mice, whereas memory-phenotype CD4(+) T cells (CD62L(low)/CD44(high)) are present at reduced numbers in the periphery. These results indicate that CARMA1 is essential for Treg development, but is not necessary for the development of other agonist-selected T-cell subsets. Overall, these data reveal an important but differential role for CARMA1-mediated TCR signaling in T-cell development.
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02114, USA. bmedoff@partners.org
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Medoff
authors.forename: Barry P
authors.initials: BP
authors.lastname: Sandall
authors.forename: Aimee
authors.initials: A
authors.lastname: Landry
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Nagahama
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mizoguchi
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Luster
authors.forename: Ramnik J
authors.initials: RJ
authors.lastname: Xavier
mesh_terms: D000818:Animals; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000819:agonists / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D053468:CARD Signaling Adaptor Proteins; C496467:Card11 protein, mouse; D011948:Receptors, Antigen, T-Cell