Myelin proteolipid protein-specific CD4+CD25+regulatory cells mediate genetic resistance to experimental autoimmune encephalomyelitis
- 18 October 2004
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 101 (43), 15434-15439
- https://doi.org/10.1073/pnas.0404444101
Abstract
SJL mice are highly susceptible to experimental autoimmune encephalomyelitis (EAE) induced with myelin proteolipid protein (PLP) peptide 139-151, whereas H-2 congenic B10.S mice are resistant. Immunodominance and susceptibility to EAE are associated with a high precursor frequency of PLP 139-151-specific T cells in the naive repertoire of SJL mice. To understand the mechanism of EAE resistance in B10.S mice, we determined the precursor frequency of PLP 139-151-reactive T cells in both strains by using IAs/PLP 139-151 tetramers. SJL and B10.S mice had similar frequencies of tetramer-reactive T cells in the naive peripheral repertoire. However, in SJL mice, the majority of PLP 139-151 tetramer-positive cells were in the CD4+CD25- population, whereas there were more tetramer-positive cells in the CD4+CD25+ population of B10.S mice. Depletion of CD4+CD25+ cells in vivo facilitated the expansion of PLP 139-151-reactive cells with production of T helper 1 cytokines in EAE-resistant B10.S mice. Furthermore, anti-CD25 Ab treatment before immunization resulted in EAE induction in these otherwise resistant mice. These data indicate an important role for autoantigen-specific CD4+CD25+ cells in genetic resistance to autoimmunity.Keywords
This publication has 27 references indexed in Scilit:
- An essential role for Scurfin in CD4+CD25+ T regulatory cellsNature Immunology, 2003
- Control of Regulatory T Cell Development by the Transcription Factor Foxp3Science, 2003
- Thymic Selection Generates a Large T Cell Pool Recognizing a Self-Peptide in HumansThe Journal of Experimental Medicine, 2002
- Major Histocompatibility Complex Class II–Positive Cortical Epithelium Mediates the Selection of Cd4+25+ Immunoregulatory T CellsThe Journal of Experimental Medicine, 2001
- Certified ProfessionalsThe Journal of Experimental Medicine, 2001
- Regulatory T CellsCell, 2000
- Regulation of Interleukin (IL)-12 Receptor β2 Subunit Expression by Endogenous IL-12: A Critical Step in the Differentiation of Pathogenic Autoreactive T CellsThe Journal of Experimental Medicine, 1999
- IL-12 unmasks latent autoimmune disease in resistant mice.The Journal of Experimental Medicine, 1996
- An altered peptide ligand mediates immune deviation and prevents autoimmune encephalomyelitisImmunity, 1995
- Acute autoimmune encephalomyelitis in mice. II. Susceptibility is controlled by the combination of H-2 and histamine sensitization genes.The Journal of Experimental Medicine, 1982