The inhibitory function of B7 costimulators in T cell responses to foreign and self-antigens.
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.
Lohr
Jens
J
Department of Pathology, University of California San Francisco School of Medicine, San Francisco, California 94143-0511, USA.
Knoechel
Birgit
B
Jiang
Shuwei
S
Sharpe
Arlene H
AH
Abbas
Abul K
AK
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000502:physiology; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity; D018122:B7-1 Antigen / Q000502:physiology*; D060908:CTLA-4 Antigen; D005260:Female; D018796:Immunoconjugates; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D001324:Autoantigens; D018122:B7-1 Antigen; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D015375:Receptors, Interleukin-2; D000069594:Abatacept; D010047:Ovalbumin