A role for the B7-1/B7-2:CD28/CTLA-4 pathway during negative selection.
Although costimulation plays an important role in activating naive T cells, its role in negative selection is controversial. By following thymocyte deletion induced by endogenous superantigens in mice lacking B7-1 and/or B7-2, we have identified a role for both B7-1 and B7-2 in negative selection. Studies using CD28-deficient and CD28/CTLA-4-double-deficient mice have revealed that either CD28 or another as yet undefined coreceptor can mediate these B7-dependent signals that promote negative selection. Finally, CTLA-4 delivers signals that inhibit selection, suggesting that CTLA-4 and CD28 have opposing functions in thymic development. Combined, the data demonstrate that B7-1/B7-2-dependent signals help shape the T cell repertoire.
Buhlmann
Janet E
JE
Department of Pathology, Immunology Research Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Elkin
Sheryl Krevsky
SK
Sharpe
Arlene H
AH
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D000943:Antigens, Differentiation / Q000235:genetics / Q000502:physiology*; D018122:B7-1 Antigen / Q000235:genetics / Q000502:physiology*; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000235:genetics / Q000502:physiology*; D019013:CD40 Antigens / Q000235:genetics / Q000502:physiology; D060908:CTLA-4 Antigen; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D017637:Clonal Deletion / Q000235:genetics / Q000276:immunology*; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D004768:Enterotoxins / Q000096:biosynthesis / Q000502:physiology; D008212:Lymphocyte Depletion; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000096:biosynthesis / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; D019013:CD40 Antigens; D060908:CTLA-4 Antigen; C497965:Cd86 protein, mouse; C556707:Ctla4 protein, mouse; D004768:Enterotoxins; D008562:Membrane Glycoproteins; D018089:Superantigens; C031818:enterotoxin B, staphylococcal