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

P>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+CD25high T cells [regulatory T cells (T-regs)] (1 center dot 9 versus 5 center dot 2, P < 0 center dot 01) and CD4+CD69+ T cells (3 center dot 2 versus 9 center dot 3, P = 0 center dot 02) and higher activity scores (4 center dot 1 versus 1 center dot 5, P = 0 center dot 01) in SLE patients with lymphopenia compared with those without lymphopenia. Lymphopenia increased the risk for decreased numbers of CD4+CD25high cells (relative risk 1 center dot 80, 95% confidence interval 1 center dot 10-2 center dot 93; P = 0 center dot 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+CD25high 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.