Cd4+ T Cell Expressed Cd80 Regulates Central Nervous System Effector Function and Survival During Experimental Autoimmune Encephalomyelitis.
From: Department of Microbiology-Immunology and Interdepartmental Immunobiology Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Journal of immunology (Baltimore, Md. : 1950)
- Publish Date: Sep 2006
- ISSN: 0022-1767
- Volume: 177
- Issue: 5
- Pages: 2948-58
- Medium: Print
- Language: English
- Citation (JAMA): Podojil Joseph R, Kohm Adam P, Miller Stephen D, et al. Cd4+ T Cell Expressed Cd80 Regulates Central Nervous System Effector Function and Survival During Experimental Autoimmune Encephalomyelitis.. J. Immunol. Sep 2006;177:2948-58
Abstract
CD80 expressed on the surface of APCs provides a positive costimulatory signal to naive CD4+ T cells during activation. Therefore, it was hypothesized that treatment of SJL mice with various forms of anti-CD80 mAb during remission from the acute phase of relapsing experimental autoimmune encephalomyelitis (R-EAE) would ameliorate disease progression. We previously reported that treatment of SJL mice with anti-CD80 Fab during R-EAE remission blocked activation of T cells specific for endogenous myelin epitopes, inhibiting epitope spreading and clinical disease progression; however, treatment with the native form of the same anti-CD80 mAb exacerbated disease progression. The current data show that intact anti-CD80 mAb binds both CNS-infiltrating CD4+ T cells and CD11c+ dendritic cells and that exacerbation of R-EAE directly correlates with increased survival and activity of myelin-specific CD4+ T cells, while the percentage of CD11c+ dendritic cells in the CNS and their APC activity was not altered. In vitro data show that cross-linking CD80 on the surface of CD4+ T cells activated in the presence of Th1-promoting cytokines increases the level of T cell activation, effector function, and survival by directly up-regulating the expression levels of transcripts for T-bet, IFN-gamma, and Bcl-xL. These findings indicate a novel regulatory role for CD80-mediated intracellular signals in CD4+ T cells and have important implications for using anti-costimulatory molecule mAb therapy in established autoimmune disease.
Mesh Headings (Keywords): Animals, Antibodies, Monoclonal, Antigen-Presenting Cells, Antigens, CD11c, Antigens, CD80, CD4-Positive T-Lymphocytes, Cell Survival, Cells, Cultured, Dendritic Cells, Encephalomyelitis, Autoimmune, Experimental, Epitopes, Female, Interferon Type II, Mice, Myelin Proteolipid Protein, Peptide Fragments, T-Box Domain Proteins, Transcription Factors, bcl-X Protein
Check for Full Text / PubMed Unique Identifier (PMID): 16920930
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