Effect of adenosine receptor subtypes stimulation on mixed lymphocyte reaction

The cell-to-cell interaction through binding of intercellular adhesion molecule (ICAM)-1 on monocytes to their ligands lymphocyte function-associated antigen (LFA)-1 on T-cells plays important roles in cytokine production and T-cell proliferation. Interleukin (IL)-18, which plasma levels are elevated in patients during acute rejection following organ transplantation, induces the expression of ICAM-1 on monocytes, production of interferon (IFN)-γ and IL-12 and lymphocyte proliferation during human mixed lymphocyte reaction. Activation of the adenosine A_2A receptor on during reperfusion of various tissues has been found to markedly reduce ischemia-reperfusion injury. In the present study, we examined the effect of adenosine at increasing concentrations ranging from 0.1 to 100 μM on the IL-18-enhanced expression of ICAM-1, production of IFN-γ and IL-12 and lymphocyte proliferation during human mixed lymphocyte reaction. Adenosine inhibited the IL-18-initiated immune responses. The IC₅₀ values of adenosine for inhibition of the IL-18-enhanced ICAM-1 expression, IFN-γ production and lymphocyte proliferation were 20 μM, respectively. The actions of adenosine depended on the stimulation of adenosine A_2A receptor. An inhibitor of protein kinase A (PKA) at 100 μM inhibited the actions of adenosine, suggesting that PKA might be involved in the actions of adenosine. On the other hand, the stimulation of adenosine A₁ and A₃ receptor blocked the actions of adenosine A_2A receptor stimulation. These results suggest that adenosine inhibits the immune responses during mixed lymphocyte reaction via adenosine A_2A receptor.