Altered homeostasis of CD4 + FoxP3 + regulatory T-cell subpopulations in systemic lupus erythematosus
Journal
Immunology
Journal Volume
127
Journal Issue
2
Pages
196-205
Date Issued
2009
Author(s)
Abstract
The role of naturally occurring regulatory T cells (Treg), known to be phenotypically heterogeneous, in controlling the expression of systemic lupus erythematosus (SLE) is incompletely defined. Therefore, different subpopulations of CD4 + FoxP3 + Tregs in patients with active or inactive SLE were investigated and compared with those of healthy subjects and patients with ankylosing spondylitis (AS). Characterization of different subsets of circulating CD4 + FoxP3 + Tregs was examined using flow cytometry. CD4 + CD25 high T cells were sorted and examined for suppressive activity in vitro. The results showed first that a significant decrease in the frequency of CD4 + CD25 high FoxP3 + T cells was present in patients with active SLE (n = 58), compared with healthy controls (n = 36) and AS patients (n = 23). In contrast, the frequencies of CD25 low FoxP3 + and CD25 - FoxP3 + CD4 + T cells were significantly increased in patients with active SLE by comparison with the control subjects. The elevation of these two putative Treg subpopulations was associated with lower plasma levels of complement C3 and C4 in patients with SLE. In addition, the ratios of the three subsets of CD4 + FoxP3 + Tregs versus effector T cells (CD4 + CD25 + FoxP3 -) were inversely correlated with the titer of anti-double-stranded DNA IgG in patients with inactive, but not active, SLE. These results suggest that the pathogenesis of SLE may be associated with a defect in the homeostatic control of different Treg subsets. ? 2008 Blackwell Publishing Ltd.
Subjects
Anti-dsDNA IgG; FoxP3; Regulatory T cells; Systemic lupus erythematosus
SDGs
Other Subjects
azathioprine; complement component C3; complement component C4; DNA; double stranded DNA antibody; hydroxychloroquine; immunoglobulin G; immunoglobulin G antibody; prednisolone; transcription factor FOXP3; adult; aged; ankylosing spondylitis; antibody titer; article; CD25+ T lymphocyte; CD4+ CD25+ T lymphocyte; comparative study; complement blood level; controlled study; correlation analysis; double stranded DNA break; effector cell; female; flow cytometry; homeostasis; human; in vitro study; lymphocyte count; major clinical study; male; pathogenesis; priority journal; regulatory T lymphocyte; systemic lupus erythematosus; T lymphocyte subpopulation; Adult; Aged; Antibodies, Antinuclear; Cell Proliferation; Cells, Cultured; Disease Progression; DNA; Female; Forkhead Transcription Factors; Homeostasis; Humans; Immunoglobulin G; Immunophenotyping; Interleukin-2 Receptor alpha Subunit; Lupus Erythematosus, Systemic; Male; Middle Aged; T-Lymphocyte Subsets; T-Lymphocytes, Regulatory; Young Adult
Type
journal article