The Role And Mechanism Of Costimulatory Signals And Related Cytokines In Acute Renal Allograft Rejection

The acute rejection mediated by T cells often happens during allogenic renal transplantations. Two signals are necessary for the activation of T cells: (1) MHC-antigen complex presented by antigen-presenting cells (APC), the first signal; (2)Costimulatory signals provided by APC, second signal. Patients with allogenic renal transplantation were studied in this research. The costimulatory molecules expressed by T cells were analyzed by flow cytometry during acute rejection stage. The inhibitory effect of the anti-costimulatory molecules mAbs on allogenic mixed lymphocyte reaction was measured by 3H-TdR incorporation; Concentrations of IL-2 and sIL-2R in serum were analyzed by ELISA. Results: An upregulating expression of costimulatory molecules, including CD40, CD40L, CD80 and 4-IBB, was detected on T cells accompanied by acute renal allograft rejection. CD25, CD86 and OX40 were expressed high as well; Proliferation of T cells was inhibited by the anti-CD40L or anti-CD80 mAbs; and an increasing level of IL-2 and sIL-2R was found in plasma of the patients with acute allograft rejection. It suggests that expression of CD40, CD40L, CD80, 4-IBB, IL-2and sIL-2R may have a potential use for the early stage diagnosis of acute allograft rejection. Blockade mAbs to CD40L and CD80 will be expected to interfere in immunity of acute allogenic renal rejection.