Research On The Relationship Between Costimulatory Signal4-1BBL/4-1BB And The Pathogenesis Of Systemic Lupus Erythematosus

Objective: To observe the expression of4-1BB、CD40L on T lymphocytes and4-1BBL、CD40on B lymphocytes of patients with systemic lupus erythematosus(SLE), observe the change of the costimulatory molecule after the4-1BBL/4-1BBpathway blocked;To investigate the effect of costimulatory signal4-1BBL/4-1BB inthe proliferation, activation and apoptosis of T lymphocytes and the productions ofcytokines of SLE patients; To investigate the effect of costimulatory signal4-1BBL/4-1BB in the proliferation and apoptosis of B lymphocytes, Furtherinvestigation revealed that the relationship between costimulatory signal4-1BBL/4-1BB and the pathogenesis of SLE. Methods: The peripheral bloodlymphocytes were stimulated with anti-CD3and Mouse F(ab’)2Anti-HumanIgM,besides, the costimulatory signal of4-1BBL/4-1BB was blocked by anti-4-1BBL;the expression of4-1BB、CD40L on T lymphocytes and4-1BBL、CD40on Blymphocytes was determined by flow cytometry (FCM);The expression of4-1BBLmRNA was detected by RT-PCR. The effect of the proliferation, activation andapoptosis of peripheral blood lymphocytes was determined by Methy thiazoytetralium (MTT) and FCM. The productions of cytokines of IFN-γ and IL-4wereanalyzed by FCM.The production of soluble(s) forms of4-1BB (s4-1BB) and4-1BBL(s4-1BBL) in peripheral blood of SLE patients was determined by enzyme linkedimmunosorbent assay (ELISA). Results: The expression of4-1BB、CD40L on T cellsand4-1BBL、CD40on B cells of SLE patients was significantly higher than healthycontrols (P<0.05); There were more expression of4-1BB and CD40Lon the Tlymphocytes stimulated by anti-CD3monoantibody in SLE patients than healthycontrols （P<0.05）, With the anti-4-1BBL monoantibody blocked, there were decreased expression of4-1BB and CD40L on T lymphocytes (P<0.05); There weremore expression of4-1BBL and CD40on the B lymphocytes after stimulated byMouse F(ab’)2Anti-Human IgM for48h in SLE patients than healthy controls（P<0.05）; The production of s4-1BB and s4-1BBL in peripheral blood of SLEpatients was more than controls（P<0.05）, and the production was significantlydecreased after the4-1BBL/4-1BB pathway blocked（P<0.05）. Conclusion: Theexpression of costimulatory molecule of the peripheral blood lymphocytes wasincreased, the costimulatory signal4-1BBL/4-1BB have more effect on proliferation,activation, apoptosis of the lymphocytes and the production of cytokine of SLEpatients.