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

Clin Exp Immunol. 2011 Apr;164(1):17-25. doi: 10.1111/j.1365-2249.2010.04309.x. Epub 2011 Jan 14.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / immunology
  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte / immunology
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • Azathioprine / therapeutic use
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cells, Cultured
  • Female
  • Flow Cytometry
  • Follow-Up Studies
  • Humans
  • 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
  • Lymphopenia / complications
  • Lymphopenia / immunology*
  • Male
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • Time Factors
  • Young Adult


  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • Immunosuppressive Agents
  • Interleukin-2 Receptor alpha Subunit
  • Lectins, C-Type
  • Azathioprine