Abstract
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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Allan, S.E., Passerini, L., Bacchetta, R., Crellin, N., Dai, M., Orban, P.C., Ziegler, S.F., Roncarolo, M.G. and Levings, M.K. (2005) The role of 2 FOXP3 isoforms in the generation of human CD4+ Tregs. J. Clin. Invest. 115, 3276–3284.
Alvarado-Sanchez, B., Hernandez-Castro, B., Portales-Perez, D., Baranda, L., Layseca-Espinosa, E., Abud-Mendoza, C., Cubillas-Tejeda, A.C. and Gonzalez-Amaro, R. (2006) Regulatory T cells in patients with systemic lupus erythematosus. J. Autoimmun. 27, 110–118.
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.
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.
Chen, Z., Herman, A.E., Matos, M., Mathis, D. and Benoist, C. (2005) Where CD4+CD25+ T reg cells impinge on autoimmune diabetes. J. Exp. Med. 202, 1387–1397.
Crispin, J.C., Martinez, A. and Alcocer-Varela, J. (2003) Quantification of regulatory T cells in patients with systemic lupus erythematosus. J. Autoimmun. 21, 273–276.
Fontenot, J.D., Gavin, M.A. and Rudensky, A.Y. (2003) Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat. Immunol. 4, 330–336.
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.
Hori, S., Takahashi, T. and Sakaguchi, S. (2003) Control of autoimmunity by naturally arising regulatory CD4+ T cells. Adv. Immunol. 81, 331–371.
Kriegel, M.A., Lohmann, T., Gabler, C., Blank, N., Kalden, J.R. and Lorenz, H.M. (2004) Defective suppressor function of human CD4+ CD25+ regulatory T cells in autoimmune polyglandular syndrome type II. J. Exp. Med. 199, 1285–1291.
Lee, J.H., Wang, L.C., Lin, Y.T., Yang, Y.H., Lin, D.T. and Bhiang, B.L. (2006) Inverse correlation between CD4+ regulatory T cell population and autoantibody levels in paediatric patients with systemic lupus erythematosus. Immunology 117, 280–286.
Lindley, S., Dayan, C.M., Bishop, A., Roep, B.O., Peakman, M. and Treem T.I. (2005) Defective suppressor function in CD4(+)CD25(+) T cells from patients with type 1 diabetes. Diabetes 54, 92–99.
Liu, M.F., Wang, C.R., Fung, L.L. and Wu, C.R. (2004) Decreased CD4+CD25+ T cells in peripheral blood of patients with systemic lupus erythematosus. Scand. J. Immunol. 59, 198–202.
Lyons, A.B. (2000) Analyzing cell division in vivo and in vitro using flow cytometric measurement of CFSE dye dilution. J. Immunol. Methods 243, 147–154.
Miyara, M., Amoura, Z., Parizot, C., Badoual, C., Dorgham, K., Trad, S., Nochy, D., Debre, P., Piette, J.C. and Gorochov, G. (2005) Global natural regulatory T cell depletion in active systemic lupus erythematosus. J. Immunol. 175, 8392–8400.
Read, S., Greenwald, R., Izcue, A., Robinson, N., Mandelbrot, D., Francisco, L., Sharpe, A.H. and Powrie, F. (2006) Blockade of CTLA-4 on CD4+CD25+ regulatory T cells abrogates their function in vivo. J. Immunol. 177, 4376–4383.
Schubert, L.A., Jeffery, E., Zang, Y., Ramsdell, F. and Ziegler, S.F. (2001) Scurfin (FOXP3) acts as a repressor of transcription and regulates T cell activation. J. Biol. Chem. 276, 37672–37679.
Shevach, E.M. (2001) Certified professionals: CD4(+)CD25(+) suppressor T cells. J. Exp. Med. 193, F41–F46.
Suarez, A., Lopez, P., Gomez, J. and Gutierrez, C. (2006) Enrichment of CD4+ CD25high T cell population in patients with systemic lupus erythematosus treated with glucocorticoids. Ann. Rheum. Dis. 65, 1512–1517.
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.
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.
Viglietta, V., Baecher-Allan, C., Wiener, H.L. and Hafler, D.A. (2004) Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis. J. Exp. Med 199, 971–979.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2007 Springer Science+Business Media, LLC
About this paper
Cite this paper
Lyssuk, E.Y., Torgashina, A.V., Soloviev, S.K., Nassonov, E.L., Bykovskaia, S.N. (2007). Reduced Number and Function of CD4+ CD25 high FoxP3 + Regulatory T Cells in Patients with Systemic Lupus Erythematosus. In: Shurin, M.R., Smolkin, Y.S. (eds) Immune-Mediated Diseases. Advances in Experimental Medicine and Biology, vol 601. Springer, New York, NY. https://doi.org/10.1007/978-0-387-72005-0_12
Download citation
DOI: https://doi.org/10.1007/978-0-387-72005-0_12
Publisher Name: Springer, New York, NY
Print ISBN: 978-0-387-72004-3
Online ISBN: 978-0-387-72005-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)