@article {542646, title = {The inhibitory function of B7 costimulators in T cell responses to foreign and self-antigens.}, journal = {Nat Immunol}, volume = {4}, number = {7}, year = {2003}, month = {2003 Jul}, pages = {664-9}, abstract = {When antigen-presenting cells (APCs) encounter inflammatory stimuli, they up-regulate their expression of B7. A small amount of B7 is also constitutively expressed on resting APCs, but its function is unclear. Here we show that initiation of T cell responses requires the expression of B7 on immunizing APCs, but the responses are much greater in the absence of basal B7 expression. Transfer of antigen-specific CD4+CD25+ cells reverses the increased responsiveness, and tolerance to a self-protein is broken by immunization in the absence of basal B7, thereby inducing autoimmunity. Similar loss of self-tolerance is seen on depletion of CD25+ cells. Thus, constitutively expressed B7 costimulators function to suppress T cell activation and maintain self-tolerance, principally by sustaining a population of regulatory T cells.}, keywords = {Animals, Antigens, CD, Antigens, CD80, Antigens, Differentiation, Autoantigens, Autoimmunity, CTLA-4 Antigen, Female, Immunoconjugates, Male, Mice, Mice, Inbred BALB C, Ovalbumin, Receptors, Interleukin-2, T-Lymphocytes, T-Lymphocytes, Helper-Inducer}, issn = {1529-2908}, doi = {10.1038/ni939}, author = {Lohr, Jens and Knoechel, Birgit and Jiang, Shuwei and Sharpe, Arlene H and Abbas, Abul K} }