A role for CTLA-4-mediated inhibitory signals in peripheral T cell tolerance?
Occupancy of the antigen receptor is not sufficient for activation of naïve T cells--additional co-stimulatory signals are required that can be provided only by 'professional' antigen-presenting cells. This two-signal model for T cell activation has been thought to provide a mechanism for the induction and maintenance of peripheral tolerance. Work over the past six years has demonstrated that the relevant co-stimulatory receptor on T cells is the molecule CD28. Recent data shows that the CD28 homologue CTLA-4 plays a role in negative regulation of T cell responses. Here we suggest that CTLA-4 may also serve as an attenuator of T cell-activating signals, raising the threshold of stimulation required to obtain full activation. The inhibitory signals mediated by CTLA-4 may provide an additional mechanism for the maintenance of peripheral tolerance.
Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley 94720-3200, USA.
J P
JP
Allison
C
C
Chambers
A
A
Hurwitz
T
T
Sullivan
B
B
Boitel
S
S
Fournier
M
M
Brunner
M
M
Krummel
D000069594:Abatacept; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism*; D018106:CD28 Antigens / Q000378:metabolism; D060908:CTLA-4 Antigen; D007108:Immune Tolerance; D018796:Immunoconjugates; D007166:Immunosuppressive Agents / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D000069594:Abatacept