The CD28-related molecule ICOS is required for effective T cell-dependent immune responses.
While CD28 is critical for expansion of naive T cells, recent evidence suggests that the activation of effector T cells is largely independent of CD28/B7. We suggest that ICOS, the third member of the CD28/CTLA-4 family, plays an important role in production of IL-2, IL-4, IL-5, and IFNgamma from recently activated T cells and contributes to T cell-dependent B help in vivo. Inhibition of ICOS attenuates lung mucosal inflammation induced by Th2 but not Th1 effector populations. Our data indicate a critical function for the third member of the CD28 family in T cell-dependent immune responses.
Department of Biology, Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts 02139, USA. coyle@mpi.com
A J
AJ
Coyle
S
S
Lehar
C
C
Lloyd
J
J
Tian
T
T
Delaney
S
S
Manning
T
T
Nguyen
T
T
Burwell
H
H
Schneider
J A
JA
Gonzalo
M
M
Gosselin
L R
LR
Owen
C E
CE
Rudd
J C
JC
Gutierrez-Ramos
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology*; D060908:CTLA-4 Antigen; D003001:Cloning, Molecular; D016207:Cytokines / Q000096:biosynthesis; D015870:Gene Expression; D006801:Humans; D018796:Immunoconjugates; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D060889:Inducible T-Cell Co-Stimulator Protein; D019169:Jurkat Cells; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; D016207:Cytokines; C556692:ICOS protein, human; C556694:Icos protein, mouse; D018796:Immunoconjugates; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D060889:Inducible T-Cell Co-Stimulator Protein; D000069594:Abatacept