CD4 T lymphocyte subsets display heterogeneous susceptibility to apoptosis induced by serum from patients with systemic lupus erythematosus

Abstract

Abstract Background: Serum from systemic lupus erythematosus (SLE) patients has been shown to induce T-lymphocyte (TL) apoptosis. Given that different cells of the immune system display different sensitivity to apoptosis, we set to evaluate the in vitro effect of SLE serum on regulatory T-cells (Treg), Th17, Th1 and Th2 from SLE patients and healthy controls. Methods: Peripheral blood mononuclear cells from SLE patients or normal controls were exposed to a pool of sera from SLE patients or normal controls. Annexin V was used to label cells in apoptosis or necrosis. Annexin V-labeled Treg, Th17, Th1 and Th2 cells were determined using flow cytometry. Results: Total CD3+ and CD4+ cells from SLE patients showed higher frequency of spontaneous apoptosis/necrosis than cells from controls, whereas Th1 cells from SLE patients presented reduced spontaneous apoptosis/necrosis rate as compared with cells from controls. Total CD3+ and CD4+ cells from normal controls incubated with SLE serum presented increased frequency of apoptotic/necrotic cells as compared with cultures incubated with normal human serum (NHS) or without human serum at all. Treg cells from SLE patients were more prone to apoptosis/necrosis induced by SLE serum than Treg cells from normal individuals. Incubation with SLE serum did not increase the apoptosis/necrosis rate in Th1, Th2 or Th17 cells. Th1 and Th17 cells presented increased apoptosis rates in cultures without human serum. Conclusion: Our findings indicate that the serum of patients with active SLE stimulates apoptosis of CD4+ T cells in general and exhibit differentiated effects on CD4+ T-cell subsets.