Costimulatory signal blockade in murine relapsing experimental autoimmune encephalomyelitis.
Blockade of the CD28-B7 or CD40L-CD40 T cell costimulatory signals prevents induction of experimental autoimmune encephalomyelitis (EAE). However, the effect of simultaneous blockade of these signals in EAE is unknown. We show that administration of either MR1 (to block CD40L) or CTLA4Ig (to block B7) after immunization or after the first attack protects from EAE. Treatment with a combination of CTLA4Ig and MR1 provides additive protection, and is associated with complete absence of mononuclear cell infiltrates in the central nervous system, and marked suppression of proliferation of primed T cells in the periphery. Selective B7-1 blockade did not protect from EAE. These observations have implications for therapy of autoimmune diseases.
Schaub
M
M
Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Issazadeh
S
S
Stadlbauer
T H
TH
Peach
R
R
Sayegh
M H
MH
Khoury
S J
SJ
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000494:pharmacology; D018122:B7-1 Antigen / Q000494:pharmacology*; D018106:CD28 Antigens / Q000494:pharmacology*; D023201:CD40 Ligand; D060908:CTLA-4 Antigen; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004357:Drug Synergism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D018796:Immunoconjugates; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D004676:Myelin Basic Protein / Q000494:pharmacology; D012008:Recurrence; D015398:Signal Transduction / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects; D013997:Time Factors
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D008562:Membrane Glycoproteins; D004676:Myelin Basic Protein; D023201:CD40 Ligand; D000069594:Abatacept