Objective: To detect the effects of leflunomide to phenotype and function of dendritic cells (DCs) in systemic lupus erythematosus (SLE) patients, reveal the effective mechanism inducing remission of SLE and lay a research foundation for using 'inhibit' DCs to treat SLE in future.
Methods: The monocytes were isolated from peripheral blood of SLE patients and cultivated into DCs with cytokines such as GM-CSF and IL-4. A771726 (active metabolite) was added in with cytokines in leflunomide group, but not in control. DCs were harvested after 9 days culture. CD(80), CD(83), CD(86) and HLA-DR surface markers on DCs were detected by flow cytometry (FACS). The ability of DCs stimulating lymphocytes proliferation was detected by MTT assay. IL-10 and IFNgamma level in the supernatant of MLR were detected by ELISA and T cell subtype after MLR was detected by FACS.
Results: The DCs treated with A771726 showed a lower percentage expression of CD(83), CD(86) and HLA-DR phenotype (CD(83): 72.70 +/- 1.77 vs. 79.36 +/- 4.80, CD(86): 63.50 +/- 14.06 vs. 83.91 +/- 9.81, HLA-DR: 80.44 +/- 12.56 vs. 90.51 +/- 8.63, all P < 0.01), a weaker ability to stimulating T lymphocytes proliferation (at DC:TC = 1:10, 0.285 +/- 0.079 vs. 0.458 +/- 0.100; at DC:TC = 1:50, 0.194 +/- 0.054 vs. 0.382 +/- 0.023, all P < 0.01) and a lower secretive level of IL-10 in the MLR supernatant [(195.0 +/- 36.9) microg/L vs. (423.6 +/- 93.2) microg/L, P < 0.01], exclude those it could still increase amount of a new T cell subtype--CD(4)(+)CD(25)(+)CTLA(4)(+) T cell (12.00% & 6.23%).
Conclusions: A771726 can inhibit DCs maturation, the immature DCs can inhibit T cells proliferation and refrain T cells from dividing into Th(2) subtype, and also the immature DCs can induce a sort of regulate T cell (CD(4)(+)CD(25)(+)CTLA(4)(+) T cell) production. Through that LEF may correct part over humor immune dysfunction and get a new immune balance in SLE.