Regulation of CD8+regulatory T cells: Interruption of the NKG2A–Qa-1 interaction allows robust suppressive activity and resolution of autoimmune disease
- 9 December 2008
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 105 (49), 19420-19425
- https://doi.org/10.1073/pnas.0810383105
Abstract
Regulation of autoreactive CD4 T cells is essential to maintain self-tolerance and prevent autoimmune disease. Although CD8 T regulatory (Treg) cells that recognize self-peptides restricted by Qa-1 (HLA-E in humans) inhibit autoreactive CD4 cells and attenuate experimental autoimmune encephalomyelitis (EAE), the mechanism of this interaction is unclear. We generated Qa-1 mutant knock-in mice that impair Qa-1 binding to the T cell receptor (TCR) and CD94/NKG2A receptors. Analysis of these mice showed that TCR-dependent recognition of Qa-1-peptide complexes on target CD4 cells is essential for suppression by CD8 Treg cells. Further analysis revealed that genetic disruption of the Qa-1-CD94/NKG2A interaction unleashes robust CD8 Treg cell activity that completely abolishes development of EAE.Keywords
This publication has 20 references indexed in Scilit:
- Isolation and characterization of CD8+ regulatory T cells in multiple sclerosisJournal of Neuroimmunology, 2008
- Perceiving the avidity of T cell activation can be translated into peripheral T cell regulationProceedings of the National Academy of Sciences of the United States of America, 2007
- Regulation of Activated CD4+ T Cells by NK Cells via the Qa-1–NKG2A Inhibitory PathwayImmunity, 2007
- Foxp3+CD25+CD4+ natural regulatory T cells in dominant self‐tolerance and autoimmune diseaseImmunological Reviews, 2006
- The immunoregulatory effects of Qa‐1Immunological Reviews, 2006
- Analysis of regulatory CD8 T cells in Qa-1-deficient miceNature Immunology, 2004
- Inhibitory NK-cell receptors on T cells: witness of the past, actors of the futureNature Reviews Immunology, 2004
- Myelin Oligodendrocyte Glycoprotein–specific T Cell Receptor Transgenic Mice Develop Spontaneous Autoimmune Optic NeuritisThe Journal of Experimental Medicine, 2003
- CD94-NKG2A receptors regulate antiviral CD8+ T cell responsesNature Immunology, 2002
- The Igκ 3′ Enhancer Influences the Ratio of Igκ versus Igλ B LymphocytesImmunity, 1996