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Mol Immunol. 2009 Apr;46(7):1432-42. doi: 10.1016/j.molimm.2008.12.010. Epub 2009 Feb 5.

Mutual activation of CD4+ T cells and monocytes mediated by NKG2D-MIC interaction requires IFN-gamma production in systemic lupus erythematosus.

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  • 1The Institute of Immunology, PLA, Third Military Medical University, Chongqing 400038, PR China.

Abstract

The activating receptor NKG2D is mainly expressed by human CD8(+) T cells and NK cells but normally absent on CD4(+) T cells. However, a subset of autoreactive NKG2D(+)CD4(+) T cells has been found to exist in some autoimmune disease such as rheumatoid arthritis (RA) and to participate in the imbalance of immune response and inflammation. Up to date this observation has been extended to some autoimmune diseases such as RA and Crohn's disease and the mechanism underlying the presence of this type of NKG2D(+)CD4(+) T cells has not been delineated yet. In this study, we found that a substantial proportion of CD4(+) T cells expressed NKG2D in the PBMC of SLE patients. We also found that monocytes in SLE aberrantly expressed the NKG2D ligand of MHC class I chain-related (MIC) molecules and membrane-bound IL-15 (mIL-15) at the cell surface. When cultured with the sera from SLE patients, the monocytes from healthy volunteers could be induced to express MIC and mIL-15. However, this induced expression of MIC and mIL-15 could be blocked with anti-IFN-gamma receptor (anti-IFN-gammaR) antibody. We further demonstrated that NKG2D could be induced on normal CD4(+) T cells either cocultured with monocytes from patients with SLE, or monocytes from healthy volunteers but pretreated with IFN-gamma. Moreover, Th1 cytokines were found to be produced by NKG2D(+)CD4(+) T cells in the coculture system. By transwell assay, we found that both NKG2D expression and Th1 cytokines production depended on the cell-cell contact. These results indicate that the elevated sera IFN-gamma may be responsible for MIC and mIL-15 induction on monocytes in SLE; mIL-15 on monocytes contribute to NKG2D receptor induction on a subset of CD4(+) T cells. Moreover, CD14(+) monocytes promote NKG2D(+)CD4(+) T cells activation through the NKG2D-MIC engagement in the pathogenesis of SLE.

PMID:
19200602
[PubMed - indexed for MEDLINE]
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