Effect Of γδT Cells And Its Functional Cytokine In SLE And RA

Background: Systemic autoimmune disease means that the body’s own antigenscan make immune response to itself and lead to multiple organ and system damage.SLE (systemic lupus erythematosus, SLE) and rheumatoid arthritis (rheumatoid arthritis,RA) are two of the most common and typical system autoimmune disease. SLE is adiffuse systemic autoimmune disease, injuring several of systems and organs, having ahigh prevalence and mortality, resulting in great damage to society and family. RA is achronic autoimmune disease characterized by multi-joint synovitis, which mayeventually lead to joint deformity; it is a disease with high morbidity and the primarydisease that caused loss of labor ability and disability in China. Currently, thepathogenesis of SLE and RA is not yet entirely clear, leading to the difficulty intreatment.γδT cells are special lymphocyte cells distinguished from αβT cells in peripheralblood with a small proportion which secreting interleukin-17, interferon and tumornecrosis factor. Currently, γδT cell research mainly focused on aspects of infection,cancer and skin diseases, the studies about SLE and RA are still rare. So, γδT cellresearch has important clinical significance on the development and treatment of SLEand RA.Aim: To study the expressions of γδT cells and its functional cytokines IL-17、IFN-γ、TNF in RA and SLE could explore its role in the pathogenesis of systemicautoimmune disease.Method: The frequencies of peripheral blood γδT cells and the concentrations ofserum IL-17、IFN-γ and TNF in RA, SLE patients and healthy controls (HC) werecharacterized by flow cytometry analysis and Flow cytometric bead array (CBA). Thepotential association between them and clinical measures was analyzed. In addition, thedynamic changes on the frequency of these cells and cytokines in patients before andafter drug treatment were determined.Results:1. The frequencies of peripheral blood γδT cells, γ9δT cells andCD4-CD8-γδT cells in SLE patients were significantly lower than that in healthy controls. After the hormones and immunosuppressive therapy, these cells gradually rise,especially in the drug well-response group.2. The levels of IFN-γ, TNF and IL-17secreted by γδT cells, γ9δT cells andCD4-CD8-γδT cells in SLE patients were significantly lower than that in healthycontrols. After the therapy, these factors gradually rise, especially in the drugwell-response group.3. The concentration of serum IL-6, IL-10and IL-17were higher than that inhealthy controls in SLE patients. After the therapy, the level of IL-17gradually falls.4. Positive correlations were found between the concentration of serum C3and thelevel of IL-2, TNF, γδT cells, γ9TCR-γδT cells, CD27+γδT cells, CD4-CD8-γδT cells,IL-17+CD4-CD8-γδT cells, CD27+CD4-CD8-γδT cells in SLE patients. Negativecorrelations were found between the concentration of serum C3and the level of IL-10and IL-17. Positive correlations were found between the SLEDAI score and the level ofTNF+γδT cells, TNF+γ9δT cells. Negative correlations were found between theSLEDAI score and the level of IL-2, CD4-CD8-γδT cells, IL17+CD4-CD8-γδT cellsand CD27+CD4-CD8-γδT cells.5. Positive correlations were found between the concentration of IL-2and the levelof CD27+γδT cells and IL-17+CD4-CD8-γδT cells in SLE patients. Negativecorrelations were found between the concentration of IL-6and the level of IL-17+γ9δTcells, IL-17+CD4-CD8-γδT cells and IFN+CD4-CD8-γ9δT cells. Negative correlationswere found between the concentration of IL-10and the level of γ9δT cells, CD27+γδTcells and IL-17+CD4-CD8-γ9δT cells. Negative correlations were found between theconcentration of IFN and the level of γ9δT cells and γ9TCR-γδT cells. Negativecorrelations were found between the concentration of TNF and the level of γδT cells,CD27+γδT cells and TNF+CD4-CD8-γδT cells.6. Positive correlations were found between the level of γδT cells and the level ofγ9δT cells, γ9TCR-γδT cells and CD4-CD8-γδT cells in SLE patients. Positivecorrelations were found between the level of γ9δT cells and the level of CD4-CD8-γ9δTcells. Positive correlations were found between the level of IFN+CD4-CD8-γ9δT cellsand the level of CD27+CD4-CD8-γ9δT cells. Positive correlations were found betweenthe level of TNF+CD4-CD8-γδT cells and the level of CD27+CD4-CD8-γδT cells.Positive correlations were found between the level of IL-17+γδT cells and the level ofTNF+γδT cells and IFN+γδT cells. Positive correlations were found between the level of IL-17+γ9δT cells and the level of IFN+γ9δT cells. Positive correlations were foundbetween the level of IL-17+CD4-CD8-γδT cells and the level of CD27+CD4-CD8-γδTcells. Positive correlations were found between the level of IL-17+CD4-CD8-γ9δT cellsand the level of IFN+CD4-CD8-γ9δT cells and CD27+CD4-CD8-γ9δT cells. Positivecorrelations were found between the level of CD27+γδT cells and the level of TNF+γδT cells. Positive correlations were found between the level of CD27+γ9δT cells andthe level of TNF+γ9δT cells and IL-17+γ9δT cells.7. The frequencies of peripheral blood γ9δT cells and CD4-CD8-γδT cells in RApatients were significantly higher than that in healthy controls. After theimmunosuppressive therapy, γ9δT cells gradually fall, especially in the drugwell-response group.8. The levels of IFN-γ secreted by γδT cells and CD4-CD8-γδT cells in RA patientswere significantly lower than that in healthy controls. The levels of TNF and IL-17secreted by γ9δT cells were significantly higher than that in healthy controls. After thetherapy, these factors gradually fall, especially in the drug poor-response group. Thelevels of IL-17secreted by CD4-CD8-γ9δT cells were significantly higher than that inhealthy controls and after treatment decreased.9. The concentration of serum IL-6, IL-10, IL-17and TNF were higher than that inhealthy controls in RA patients. After the therapy, the levels of IL-6, IL-17and TNFgradually fall.10. Positive correlations were found between the concentration of serum ESR andthe level of IL-6and IL-17+CD4-CD8-γ9δT cells in RA patients. Positive correlationswere found between the concentration of serum CPR and the level of IL-6and IFN+γδTcells. Positive correlations were found between the concentration of serum RF and thelevel of IFN+γδT cells, IFN+γδ9T cells, IFN+CD4-CD8-γ9δT cells and CD27+γδT cells.Positive correlations were found between the concentration of serum CCP and the levelof IL-4, IL-10, IL-17, IFN and TNF. Positive correlations were found between theDAS28score and the level of IL-6and IL17+CD4-CD8-γ9δT cells. Negativecorrelations were found between the DAS28score and the level of IFN+CD4-CD8-γδTcells, TNF+CD4-CD8-γδT cells and TNF+CD4-CD8-γ9δT cells.11. Positive correlations were found between the concentration of IL-2and thelevel of IFN+γ9δT cells in RA patients. Negative correlations were found between theconcentration of IL-2and the level of CD27+CD4-CD8-γδT cells. Negative correlations were found between the concentration of IL-4and the level of TNF+CD4-CD8-γ9δTcells. Negative correlations were found between the concentration of IL-17and thelevel of IFN+CD4-CD8-γδT cells and IFN+CD4-CD8-γ9δT cells. Negative correlationswere found between the concentration of IFN and the level of CD27+CD4-CD8-γδTcells and CD27+CD4-CD8-γ9δT cells.12. Positive correlations were found between the level of γδT cells and the level ofγ9δT cells, γ9TCR-γδT cells, CD27+γδT cells, CD4-CD8-γδT cells, CD27+CD4-CD8-γδT cells, IFN+γ9δT cells, CD27+γ9δT cells and CD27+CD4-CD8-γ9δT cellsin RA patients. Positive correlations were found between the level of γ9δT cells and thelevel of γ9TCR-γδT cells, IL-17+γδT cells, CD27+γδT cells, IFN+γ9δT cells, IL-17+γδTcells, CD27+γ9δT cells, IFN+CD4-CD8-γ9δT cells and CD27+CD4-CD8-γ9δT cells.Positive correlations were found between the level of IFN+γδT cells and the level ofCD27+γδT cells and CD4-CD8-γδT cells. Positive correlations were found between thelevel of TNF+γ9δT cells and the level of IFN+γ9δT cells. Positive correlations werefound between the level of IL-17+γ9δT cells and the level of CD27+γ9δT cells andCD4-CD8-γ9δT cells. Positive correlations were found between the level of IFN+CD4-CD8-γδT cells and the level of TNF+CD4-CD8-γδT cells and IL-17+CD4-CD8-γδTcells. Positive correlations were found between the level of TNF+CD4-CD8-γ9δT cellsand the level of CD27+CD4-CD8-γ9δT cells.Conclusions:1. In the pathogenicity of SLE, TNF+γδT cells, TNF+γ9δT cells andIL-17+CD4-CD8-γδT cells is particularly important, and could be as a potential targetfor the prevention or treatment of the disease.2. γ9δT cells, especially IL-17+CD4-CD8-γ9δT cells play important roles in theoccurrence and development of RA, and may provide a new direction for the preventionand treatment of sickness.3. Corticosteroids and immunosuppressive agents can adjust the abnormalexpression of γδT cell subsets and their function factors; further regulate the immunestatus of sickness.