The costimulatory molecule ICOS plays an important role in the immunopathogenesis of EAE.
The inducible costimulatory molecule (ICOS) is expressed on activated T cells and participates in a variety of important immunoregulatory functions. After the induction of experimental allergic encephalomyelitis in SJL mice with proteolipid protein (PLP), brain ICOS mRNA and protein were up-regulated on infiltrating CD3+ T cells before disease onset. ICOS blockade during the efferent immune response (9-20 days after immunization) abrogated disease, but blockade during antigen priming (1-10 days after immunization) exacerbated disease. Upon culture with PLP and compared with immunized controls, splenocytes produced either decreased interferon-gamma (IFN-gamma, in efferent blockade) or excessive IFN-gamma (in priming blockade). PLP-specific immunoglobulin G1 was decreased in animals treated with anti-ICOS during antigen priming, but not in other groups.
Rottman
J B
JB
Millennium Pharmaceuticals, 640 Memorial Drive, Cambridge, MA 02139, USA. jrottman@mpi.com
Smith
T
T
Tonra
J R
JR
Ganley
K
K
Bloom
T
T
Silva
R
R
Pierce
B
B
Gutierrez-Ramos
J C
JC
Ozkaynak
E
E
Coyle
A J
AJ
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology; D001921:Brain / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D018991:Myelin Proteolipid Protein / Q000009:adverse effects / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
D000945:Antigens, Differentiation, T-Lymphocyte; D018122:B7-1 Antigen; D016207:Cytokines; C556694:Icos protein, mouse; D007074:Immunoglobulin G; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D018991:Myelin Proteolipid Protein; D007371:Interferon-gamma