ABSTRACT
T regulatory (Treg) cells have a key role in the pathogenesis of chronic inflammatory and autoimmune diseases. A CD4+CD69+ T cell subset has been described that behaves as Treg lymphocytes, exerting an important immune suppressive effect. In this study, we analyzed the levels and function of CD4+CD69+ Treg cells in patients with systemic lupus erythematosus (SLE). Blood samples were obtained from 22 patients with SLE and 25 healthy subjects. Levels of CD4+CD69+ Treg cells were analyzed by multiparametric flow cytometry, and their function was measured by an assay of suppression of lymphocyte activation and through the inhibition of cytokine synthesis. We found an increased percent of CD4+CD25varCD69+TGF-ß+IL-10+Foxp3- lymphocytes in patients with SLE compared to controls. In addition, a significant diminution in the suppressive effect of these cells on the activation of autologous T lymphocytes was observed in most patients with SLE. Accordingly, CD69+ Treg cells from SLE patients showed a defective capability to inhibit the release of IL-2, IL-6, IL-10, and IL-17A by autologous lymphocytes. Our findings suggest that while CD4+CD69+ Treg lymphocyte levels are increased in SLE patients, these cells are apparently unable to contribute to the downmodulation of the autoimmune response and the tissue damage seen in this condition.
Subject(s)
Antigens, CD/immunology , Antigens, CD/metabolism , Antigens, Differentiation, T-Lymphocyte/immunology , Antigens, Differentiation, T-Lymphocyte/metabolism , Lectins, C-Type/immunology , Lectins, C-Type/metabolism , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/metabolism , Adolescent , Adult , Female , Humans , Interleukin-10/metabolism , Interleukin-17/metabolism , Interleukin-2/metabolism , Interleukin-6/metabolism , Male , Middle Aged , T-Lymphocytes, Regulatory/metabolism , Young AdultABSTRACT
BACKGROUND: Rheumatoid arthritis is a chronic inflammatory disease whose cause has not been fully elucidated. However, genetic factors seem to have an important role in its pathogenesis. OBJECTIVE: We analyzed the possible association between rheumatoid arthritis and variants of the SLC11A1 gene, which encodes for NRAMP1, a protein involved in the activation of phagocytes and synthesis of proinflammatory cytokines. METHODS: In a case-control study in a Mexican Mestizo population, blood samples from 188 patients with rheumatoid arthritis and 133 healthy individuals were obtained to determine the frequency of SLC11A1 gene variants INT4 (469+14G/C or rs3731865), D543N (1730G/A or rs17235409) and 3'UTR (1729+55del4 or rs17235416) by polymerase chain reaction and restriction fragment length polymorphism. RESULTS: We found similar frequencies of INT4 and 3'UTR polymorphisms in patients and controls (p = 0.18 and 0.89, respectively). In contrast, a significantly lower frequency of the D543N polymorphism was observed in patients with rheumatoid arthritis compared to controls (p corrected = 0.016; OR: 0.48; 95% CI: 0.28-0.80). CONCLUSION: Our data suggest that the D543N variant of SLC11A1 gene has a protective effect in the development of rheumatoid arthritis, an interesting finding that has not been previously reported in any population.
