Back to Search
Start Over
TGF-β1-Mediated Control of Central Nervous System Inflammation and Autoimmunity through the Inhibitory Receptor CD26
- Source :
- Journal of Immunology, Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2007, 178 (7), pp.4632-40, Journal of Immunology, 2007, 178 (7), pp.4632-40
- Publication Year :
- 2007
- Publisher :
- The American Association of Immunologists, 2007.
-
Abstract
- The T cell marker CD26/dipeptidyl peptidase (DP) IV is associated with an effector phenotype and markedly elevated in the human CNS disorder multiple sclerosis. However, little is known about the in vivo role of CD26/DP IV in health and disease, and the underlying mechanism of its function in CNS inflammation. To directly address the role of CD26/DP IV in vivo, we examined Th1 immune responses and susceptibility to experimental autoimmune encephalomyelitis in CD26−/− mice. We show that gene deletion of CD26 in mice leads to deregulation of Th1 immune responses. Although production of IFN-γ and TNF-α by pathogenic T cells in response to myelin Ag was enhanced in CD26−/− mice, production of the immunosuppressive cytokine TGF-β1 was diminished in vivo and in vitro. In contrast to the reduction in TGF-β1 production, responsiveness to external TGF-β1 was normal in T cells from CD26−/− mice, excluding alterations in TGF-β1 sensitivity as a mechanism causing the loss of immune regulation. Natural ligands of CD26/DP IV induced TGF-β1 production in T cells from wild-type mice. However, natural ligands of CD26/DP IV failed to elicit TGF-β1 production in T cells from CD26−/− mice. The striking functional deregulation of Th1 immunity was also seen in vivo. Thus, clinical experimental autoimmune encephalomyelitis scores were significantly increased in CD26−/− mice immunized with peptide from myelin oligodendrocyte glycoprotein. These results identify CD26/DP IV as a nonredundant inhibitory receptor controlling T cell activation and Th1-mediated autoimmunity, and may have important therapeutic implications for the treatment of autoimmune CNS disease.
- Subjects :
- Central Nervous System
MESH: Mice, Mutant Strains
medicine.medical_treatment
Encephalomyelitis
MESH: Antigens, CD26
Autoimmunity
Ligands
Lymphocyte Activation
medicine.disease_cause
MESH: Down-Regulation
MESH: Transforming Growth Factor beta1
Mice
MESH: Ligands
Immunology and Allergy
MESH: Animals
Sequence Deletion
MESH: Cytokines
biology
Experimental autoimmune encephalomyelitis
MESH: Receptors, Antigen, T-Cell
MESH: Sequence Deletion
Cytokine
medicine.anatomical_structure
[SDV.IMM]Life Sciences [q-bio]/Immunology
Cytokines
Encephalomyelitis, Autoimmune, Experimental
[SDV.IMM] Life Sciences [q-bio]/Immunology
Dipeptidyl Peptidase 4
T cell
Immunology
Receptors, Antigen, T-Cell
Down-Regulation
Myelin oligodendrocyte glycoprotein
Transforming Growth Factor beta1
Immune system
Antigen
MESH: Autoimmunity
medicine
MESH: Central Nervous System
Animals
MESH: Encephalomyelitis, Autoimmune, Experimental
MESH: Lymphocyte Activation
MESH: Mice
Th1 Cells
medicine.disease
Mice, Mutant Strains
MESH: Th1 Cells
biology.protein
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 178
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi.dedup.....5644c31fd58ec7118a551fbc2bc3e4ec