Presented at:
ASHI 31st Annual Meeting, Washington, DC, October 17-21, 2005.
Precursor dendritic cell subsets in kidney allograft recipients after induction with alemtuzumab (C1H) vs Thymoglobulin (Thy) vs Daclizumab (Dac) vs a C1H recipient given donor specific stem cells (DHSC)
Carreno MR, Ciancio G, Burke GW, Cirocco R, Salman F, Mathew J, Jin Y, Miller J, Esquenazi, V.
Division of Transplantation, University of Miami; Department of Microbiology and Immunology, University of Miami; Miami Veterans Affairs Medical Center. Miami, Florida.
Introduction : Increased circulating dendritic cell subset ratios (DC2:DC1) and/or T regulatory cells (Treg) may play a role in (peripheral) transplantation tolerance. We have recently reported a significant increase of Treg (CD4+CD25+) up to one year postoperatively in renal transplant recipients treated with Alemtuzumab (C1H) vs Thymoglobulin (Thy) vs Daclizumab (Dac). We have now analyzed dendritic cell subsets, CD11c+, i.e. DC1 (%pDC1) vs CD123+, i.e. DC2 (%pDC2) and their ratios, i.e. DC2:DC1 in these recipients. We additionally compared Treg and DC2:DC1 with those of a kidney recipient given donor specific stem cells (DHSC) plus the C1H protocol during the same period.
Methods : Of 121 recipients, 41 received C1H induction together with half dose maintenance immunosuppression (IS) with Tacrolimus (Tac) (converted to Sirolimus), MMF, but no steroids; 40 received Thy and 40 received Dac. The latter two groups received full dose Tac (no sirolimus), MMF, and steroids. Four color cocktails of monoclonal antibodies (Lin-1FITC, CD123PE, HLADRwPerCP and CD11cAPC, as well as CD3FITC, CD25PE, CD45PerCP and CD4APC) were used to quantify DC-ratios and Tregs by flow cytometry pre-transplant and at monthly intervals postoperatively.
Results : Rejection free C1H patients showed a significant increase (from pre-transplant- p<0.02) in the DC2:DC1 ratios and percent of Tregs compared to rejection free Thy or Dac groups. Moreover, of most interest, a consistently (2-3 fold) higher DC ratio and Treg % was seen in the (rejection free) DHSC C1H protocol recipient. (All patients with rejection had significantly lower values.)
Conclusions : A significant increase of DC2 and reduced DC1 (>DC2:DC1 ratios), and high Treg percentages (especially in the DHSC-C1H recipient) were consistent with a rejection free course that might allow IS withdrawal. Protocol biopsy data will also be presented.