Cyclosporin but not everolimus inhibits chemokine receptor expression on CD4 + T cell subsets circulating in the peripheral blood of renal transplant recipients

Summary The peripheral chemokine receptors chemokine receptor 3 (CXCR3) and CC chemokine receptor 5 (CCR5) have been reported to be associated with allograft rejection. The impact of the expression of immunosuppressive drugs on peripherally circulating CD4 + T cell subsets after renal transplantion is unknown. Expression of CXCR3 and CCR5 was investigated by flow cytometry in 20 renal allograft recipients participating in a prospective, randomized trial (NCT00514514). Initial immunosuppression consisted of basiliximab, cyclosporin A (CsA), mycophenolate sodium and corticosteroids. After 3 months, patients were treated either with CsA, mycophenolate sodium (MPA) plus corticosteroids ( n  = 6), CsA and everolimus plus corticosteroids ( n  = 8) or CsA‐free (CsA free ) receiving everolimus, MPA and corticosteroids ( n  = 6). After initial reduction of CD4 + forkhead box protein 3 (FoxP3) + and CD4 + CD25 hi FoxP3 + regulatory T cells (T regs ) ( P  < 0·05; P  < 0·01), 3‐month post‐transplant percentages of T regs were reconstituted in CsA free and CsA lo arms compared to CsA reg 12 months post transplant. Expression of CCR5 and CXCR3 on CD4 + FoxP3 + and CD4 + FoxP3 ‐ T cells 12 months post transplant was increased in CsA free versus CsA reg . Increase in CCR5 + CXCR3 + co‐expressing CD4 + FoxP3 ‐ cells between 3 and 12 months correlated negatively with the glomerular filtration rate (GFR) slope/year [modification of diet in renal disease (MDRD); r  = −0·59, P  < 0·01]. CsA, but not everolimus, inhibits both T reg development and expression of CXCR3 and CCR5 on CD4 + T cell subsets. Increase in CCR5 + CXCR3 + co‐expressing CD4 + FoxP3 ‐ T cells is associated with early loss in allograft function.