Quantitative and functional profiles of CD4+ lymphocyte subsets in systemic lupus erythematosus patients with lymphopenia.

Autor: Gómez-Martín D; Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico., Díaz-Zamudio M, Vanoye G, Crispín JC, Alcocer-Varela J
Jazyk: angličtina
Zdroj: Clinical and experimental immunology [Clin Exp Immunol] 2011 Apr; Vol. 164 (1), pp. 17-25. Date of Electronic Publication: 2011 Jan 14.
DOI: 10.1111/j.1365-2249.2010.04309.x
Abstrakt: Lymphopenia is a common clinical manifestation in patients with systemic lupus erythematosus (SLE). However, its physiopathogenic role and the contribution of different T cell subsets in this setting have not been addressed fully. The aim of this study was to characterize T cell subsets quantitatively and functionally and their association with lymphopenia and azathioprine treatment in SLE. We included 84 SLE patients and 84 healthy controls and selected 20 patients for a 6-month longitudinal analysis. Peripheral blood mononuclear cells were isolated, and T cell subsets were analysed by flow cytometry. Functional analyses included autologous and allogeneic co-cultures of T cells. Our data show persistently lower absolute numbers of CD4(+) CD25(high) T cells [regulatory T cells (T(regs) )] (1·9 versus 5·2, P < 0·01) and CD4(+) CD69(+) T cells (3·2 versus 9·3, P = 0·02) and higher activity scores (4·1 versus 1·5, P = 0·01) in SLE patients with lymphopenia compared with those without lymphopenia. Lymphopenia increased the risk for decreased numbers of CD4(+) CD25(high) cells (relative risk 1·80, 95% confidence interval 1·10-2·93; P = 0·003). In addition, azathioprine-associated lymphopenia was characterized by decreased absolute numbers of CD4(+) CD69(+) and CD4(+) interleukin (IL)-17(+) cells compared to disease activity-associated lymphopenia. Functional assays revealed that SLE effector T cells were highly proliferative and resistant to suppression by autologous T(regs) . In summary, lymphopenia was associated with deficient numbers of CD4(+) CD25(high) and CD4(+) CD69(+) cells and resistance of effector T cells to suppression by T(regs) , which could contribute to the altered immune responses characteristic of SLE. Furthermore, azathioprine treatment was associated with decreased numbers of CD4(+) CD69(+) and CD4(+) IL-17(+) cells and diminished T(reg) suppressive activity.
(© 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.)
Databáze: MEDLINE