A critical role for B7/CD28 costimulation in experimental autoimmune encephalomyelitis: a comparative study using costimulatory molecule-deficient mice and monoclonal antibody blockade.

Abstract

The B7/CD28 pathway provides critical costimulatory signals required for complete T cell activation and has served as a potential target for immunotherapeutic strategies designed to regulate autoimmune diseases. This study was designed to examine the roles of CD28 and its individual ligands, B7-1 and B7-2, in experimental autoimmune encephalomyelitis (EAE), a Th1-mediated inflammatory disease of the CNS. EAE induction in CD28- or B7-deficient nonobese diabetic (NOD) mice was compared with the effects of B7/CD28 blockade using Abs in wild-type NOD mice. Disease severity was significantly reduced in CD28-deficient as well as anti-B7-1/B7-2-treated NOD mice. B7-2 appeared to play the more dominant role as there was a moderate decrease in disease incidence and severity in B7-2-deficient animals. EAE resistance was not due to the lack of effective priming of the myelin peptide-specific T cells in vivo. T cells isolated from CD28-deficient animals produced equivalent amounts of IFN-gamma and TNF-alpha in response to the immunogen, proteolipid protein 56-70. In fact, IFN-gamma and TNF-alpha production by Ag-specific T cells was enhanced in both the B7-1 and B7-2-deficient NOD mice. In contrast, peptide-specific delayed-type hypersensitivity responses in these animals were significantly decreased, suggesting a critical role for CD28 costimulation in in vivo trafficking and systemic immunity. Collectively, these results support a critical role for CD28 costimulation in EAE induction.

• Authors: A M Girvin, M C Dal Canto, L Rhee, B Salomon, A Sharpe, J A Bluestone, S D Miller
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 164 Issue 1 Pg. 136-43 (Jan 01 2000) ISSN: 0022-1767 [Print] United States
• PMID: 10605004 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Blocking
• Antibodies, Monoclonal
• Antigens, CD
• B7-1 Antigen
• B7-2 Antigen
• CD28 Antigens
• Cd86 protein, mouse
• Epitopes, T-Lymphocyte
• Membrane Glycoproteins
• Myelin Proteolipid Protein
• Peptide Fragments

Topics

• Amino Acid Sequence
• Animals
• Antibodies, Blocking (pharmacology)
• Antibodies, Monoclonal (pharmacology)
• Antigens, CD (immunology)
• B7-1 Antigen (genetics, immunology, physiology)
• B7-2 Antigen
• CD28 Antigens (genetics, immunology, physiology)
• Encephalomyelitis, Autoimmune, Experimental (genetics, immunology, prevention & control)
• Epitopes, T-Lymphocyte (administration & dosage, immunology)
• Female
• Hypersensitivity, Delayed (genetics, immunology)
• Immunity, Innate
• Lymphocyte Activation (genetics, immunology)
• Membrane Glycoproteins (immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Inbred NOD
• Mice, Knockout
• Molecular Sequence Data
• Myelin Proteolipid Protein (administration & dosage, immunology)
• Peptide Fragments (administration & dosage, immunology)