Duration of TCR stimulation determines costimulatory requirement of T cells.
Current models suggest that T cells that receive only signal-1 through antigenic stimulation of the T cell receptor (TCR) become anergic, but will mount an immune response when a costimulatory signal-2 is provided. Using mice deficient for an important costimulatory molecule, CD28, we show that a transient signal-1 alone, either through infection with an abortively replicating virus, or through injection of viral peptide, anergizes CD8+ T cells, demonstrating the biological relevance of T cell anergy in vivo. However, in the absence of CD28, continued presence of signal-1 alone, either through prolonged viral replication or repeated injection of peptide, prevents the induction of anergy and generates a functional T cell response in vivo.
Kündig
T M
TM
Ontario Cancer Institute, Department of Biophysics, Toronto, Canada.
Shahinian
A
A
Kawai
K
K
Mittrücker
H W
HW
Sebzda
E
E
Bachmann
M F
MF
Mak
T W
TW
Ohashi
P S
PS
D000818:Animals; D000956:Antigens, Viral / Q000008:administration & dosage / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism; D017637:Clonal Deletion; D003602:Cytotoxicity, Immunologic; D004306:Dose-Response Relationship, Immunologic; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008817:Mice, Mutant Strains; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology
D000956:Antigens, Viral; D018106:CD28 Antigens; D011948:Receptors, Antigen, T-Cell