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

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 ({"type":"clinical-trial","attrs":{"text":"NCT00514514","term_id":"NCT00514514"}}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^hiFoxP3⁺ 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_freeversus 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.