Reduced Number and Function of CD4+ CD25 high FoxP3 + Regulatory T Cells in Patients with Systemic Lupus Erythematosus
CD4+CD25+ regulatory T cells (Tregs) play an important role in maintaining tolerance to self-antigens controlling occurrence of autoimmune diseases. Recently, it has been shown that the transcription factor forkhead box P3 (FoxP3) is specifically expressed on CD4+CD25+ T cells. FoxP3 has been described as the master control gene for the development and function of Tregs. We characterized CD4+CD25+CTLA-4+FoxP3+ T cells in 43 patients with systemic lupus erythematosus (SLE). Twenty of them comprised a group of newly admitted patients with the first manifestations of the disease, and the second group included patients that were treated with cytostatics and steroids. The results revealed a significant decrease in CD4+CD25+ and CD4+CD25high T cells numbers in patients from group I compared with control and group II patients. Coexpression of FoxP3 on CD4+CD25+ T cells was significantly reduced in both groups regardless the therapy. The ability of Tregs to suppress proliferation of autologous CD8+ and CD4+ T cells was significantly reduced in both groups of patients compared to healthy donors. Our data revealed impaired production of Tregs in SLE patients that can be partly restored by conventional treatments.
Unable to display preview. Download preview PDF.
- Beacher-Allan, C., Brown, J.A., Freeman, G.J. and Hafler, D.A. (2001) CD4+CD25high regulatory cells in human peripheral blood. J. Immunol. 167, 1245–1253.Google Scholar
- Bennett, C.L., Christie, J., Ramsdell, F., Brunkow, M.E., Ferguson, P.J., Whitesell, L., Kelly, T.E., Saulsbury, F.T., Chance, P.F. and Ochs, H.D. (2001) The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat. Genet. 27, 20–21.CrossRefPubMedGoogle Scholar
- Gavin, M.A., Taogerson, T.R., Houston, E., DeRoos, P., Ho, W.Y., Stray-Pedersen, A., Ocheltree, E.L., Greenberg, P.D., Ochs, H.D. and Rudensky, A.Y. (2006) Single-cell analysis of normal and FOXP3-mutant human T cells: FOXP3 expression without regulatory T cell development. Proc. Natl. Acad. Sci. U.S.A. 103, 6659–6664.CrossRefPubMedGoogle Scholar
- Sugiyama, H., Gyulai, R., Toichi, E., Garaczi, E., Shimada, S., Stevens, S.R., McCormick, T.S. and Cooper, K.D. (2005) Dysfunctional blood and target tissue CD4+CD25high regulatory T cells in psoriasis: mechanism underlying unrestrained pathogenic effector T cell proliferation. J. Immunol. 174, 164–173.PubMedGoogle Scholar
- van Amelsfort, J.M., Jaclbs, K.M., Bijlsma, J.W., Lafeber, F.P. and Taams, L.S. (2004) CD4(+)CD25(+) regulatory T cells in rheumatoid arthritis: differences in the presence, phenotype, and function between peripheral blood and synovial fluid. Arthritis Rheum. 50, 2775–2785.CrossRefPubMedGoogle Scholar