| Background and objective systemic lupus erythematosus is a typical autoimmune disease, with multiorgan involvement, the precise pathogenesis of which remains something of a mystery. Both of genetic and environmental factors contributes to the onset of the host immune dysfunction, exposure of autoantigens and the over-response of T cells, which inspire the activation of autoeractive B cells and provoke the disease exacerbation and the production of autoantibodies. Central to the immune dysfunction in SLE is the imbalance of inhibitive and costimulative effects to T cells. Caspase 8 signaling participates in both apoptosis and activation of lymphocytes, which has double roles in the regulation of immune homeostasis. Foxp3~+CD4~+CD25~+ regulatory T cells have an important role in the control of self-reactivity, and GITR signaling exerts its costimulative function on both effector T cells and these regulatory T cells, symphony of the effects of these cells and molecules play important roles in the maintenance of immune homeostasis. And research on these immune balance-related cells and molecules is helpful to elucidate the pathogenesis of SLE and further to lay the groundwork for finding better targets of biochemical therapy to patients with SLE.Materials and Methods Analyzing samples of 40 patients with SLE (23 patients with active disease and 17 patients with inactive disease), and 19 healthy volunteers to learn the expression of immune balance-related cells and molecules. Flow cytometric determination of the surface expressions of CD69,GITR, the intracellular expression of caspase 8 in T lymphocyte subsets and the expression of Foxp3~+CD4~+CD25~+ regulatory T cells in peripheral blood from patients with SLE and healthy control. All data are analyzed by SPSS 13.0 statistics software and analyzed by one-way ANOVA, Kruskal-Wallis Test or t-test, further comparing between groups by Nemenyi Test.Results①T lymphocyte subsets expression: Compared with healthy subjects, no significance was found in the expression percentage of CD3~+CD4~+ T cells and CD3~+T cells in peripheral blood from SLE patients (P＞0.05), but the expression of CD3~+CD8~+ T cells increased significantly (P＜0.05), the ratio of CD4~+/CD8~+ decreased in SLE patients (P＞0.05). There is no significant difference in the expression of different T cell subgroups of SLE patients with different disease activity (P＞0.05).②Intracellular expression of caspase-8: Compared with healthy subjects, the expression of activated caspase-8 increased significantly in both CD3~+CD4~+ T cells and CD3~+CD8~+ T cells from active and inactive SLE patients (P＜0.05), and particularly higher in SLE patients with active disease (P＞0.05). Further analysis showed that the expression of activated caspsae-8-expressing CD3~+CD8~+T cells was higher than that of activated caspsae-8-expressing CD3~+CD4~+T cells in SLE patients irrespective of disease activity (P＜0.05).③Expression of CD69 on the surface of T cell subpopulations: CD69 was undetectable on the surface of fresh T cells. But after stimulation with Phorbol myristate acetate plus ionomycin, the expression of CD69 was up regulated vigorously. Almost all of CD3~+CD4~+T cells expressed CD69, and no difference in the percentage of CD69-expressing CD3~+CD4~+T cells was found among healthy subjects and SLE patients with different disease activity (P＞0.05). But compared with healthy subjects, the expression percentage of CD69-expressing CD3~+CD8~+T cells increased significantly both in inactive and active SLE patients (P＜0.05), and particularly a little higher in inactive SLE patients (P＞0.05).④Expression of Foxp3~+CD4~+CD25~+ regulatory T cells: The expression percentage of Foxp3~+CD4~+CD25~+ regulatory T cells in peripheral blood from inactive SLE patients and active SLE patients were obviously lower than that from healthy subjects (P＜0.05). And the expression of Foxp3~+CD4~+CD25~+ Treg was a little higher in active SLE patients than that in inactive SLE patients (P＞0.05).⑤Expression of CD4~+CD25~+ T cells: The expression percentage of CD4~+CD25~+T cells was a little higher than that in healthy subjects, but the difference was not significant (P＞0.05). ⑥Surface expression of GITR. Compared with healthy subjects, GITR expression on T cells of SLE patients increased significantly (P＜0.05). And with the development of SLE activity, its expression on CD3~+CD4~+T cell decreased (P＞0.05), but its expression on CD3~+CD8~+T cells increased (P＞0.05).Conclusions①The expression disturbance of T subsets in SLE patients, characterized by the increasing expression of CD3~+CD8~+T cells, and the elevated expression of activation marker CD69 on CD3~+CD8~+T cells indicated that CD3~+CD8~+T cells was in highly active status, and may play important role in the pathogenesis of SLE.②And we had showed that both the surface expression of Fas and the intracellular expression of caspase 3 increased especially in CD3~+CD4~+ T cells, together with the elevated intracellular expression of Caspase-8 in CD3~+CD4~+T cells, we proposed that death signals initiated by Fas-FasL ligation, mediated by caspase-8 participated in the apoptosis of CD3~+CD4~+T cells in SLE patients; But in CD3~+CD8~+T cells, surface expression of Fas and intracellular expression of active caspase-3 increased slightly in SLE patients, and both of their expressions were lower than in CD3~+CD4~+T cells. On the other hand, the intracellular expression of active caspase-8 in CD3~+CD8~+T cells from SLE patients increased significantly, and its expression in CD3~+CD8~+T cells was obviously higher than that in CD3~+CD4~+T cells, together with the higher expression of activation marker CD69 on CD3~+CD8~+T cells, we hypothesized that caspase-8 signaling might facilitate the activation and proliferation of CD3~+CD8~+T cells in SLE. ③Costimulatory signaling mediated by higher expression of GITR may be contributive to the activation and survival of CD3~+CD8~+T cells in SLE.④Impairment of the inhibitory effects induced by the lack of Foxp3~+CD4~+CD25~+ regulatory T cells may be helpful to the over-activation and proliferation of CD3~+CD8~+T cells. And the reduction of Foxp3~+CD4~+CD25~+ regulatory T cells may be induced by the higher GITR signaling in SLE patients.The up-regulation of immune reaction induced by higher expression of GITR and activated caspase-8 in T cells, and the the loss of the inhibitory effects mediated by decreasing expression of Foxp3~+CD4~+CD25~+regulatory T cells contributed to the imbalance of peripheral homeostasis and the expression disturbance of T cell subsets in SLE. |
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