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

• Published in: Clinical and experimental immunology 2011-04, Vol.164 (1), p.17-25
• Main Authors: Gómez-Martín, D, Díaz-Zamudio, M, Vanoye, G, Crispín, J.C, Alcocer-Varela, J
• Format: Article
• Language: English
• Subjects: activated T cells; Adult; Analytical, structural and metabolic biochemistry; Antigens, CD - immunology; Antigens, CD - metabolism; Antigens, Differentiation, T-Lymphocyte - immunology; Antigens, Differentiation, T-Lymphocyte - metabolism; azathioprine; Azathioprine - therapeutic use; Biological and medical sciences; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cells, Cultured; Data processing; Effector cells; Female; Flow Cytometry; Follow-Up Studies; Fundamental and applied biological sciences. Psychology; Hematologic and hematopoietic diseases; Humans; Immunoregulation; Immunosuppressive Agents - therapeutic use; Interleukin-2 Receptor alpha Subunit - immunology; Interleukin-2 Receptor alpha Subunit - metabolism; Lectins, C-Type - immunology; Lectins, C-Type - metabolism; Lupus Erythematosus, Systemic - complications; Lupus Erythematosus, Systemic - immunology; Lymphocyte Count; Lymphocytes T; Lymphopenia; Lymphopenia - complications; Lymphopenia - immunology; Male; Medical sciences; Other diseases. Hematologic involvement in other diseases; Peripheral blood mononuclear cells; Risk assessment; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Systemic lupus erythematosus; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Time Factors; Translational Studies; Tregs; Young Adult
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2010.04309.x

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 (Tregs)] (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⁺CD25high 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 Tregs. In summary, lymphopenia was associated with deficient numbers of CD4⁺CD25high and CD4⁺CD69⁺ cells and resistance of effector T cells to suppression by Tregs, 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 Treg suppressive activity.