Presented at:
American Transplant Congress
Seattle, Washington, May 21, 2005
T regulatory cells after induction therapy with Campath-1H, vs Thymoglobulin vs Daclizumab in kidney transplant recipients
Carreno M, Cirocco R, Mathew J, Ciancio G, Burke GW, Miller J, Esquenazi V
University of Miami and the VA Medical Center, Miami, FL
Introduction: T regulatory cells (Tregs) have been postulated to play an important role in the control of autoimmunity, allergy and more recently in allograft acceptance. We previously reported the effect that three distinct induction therapies have on the cell makeup in the bone marrow and peripheral blood compartments. In the present study Treg frequency was examined in the same patients (Campath-1H vs Thymoglobulin vs Daclizumab induction), in a serial monitoring protocol.
Methods: Of 121 recipients enrolled; 41 received Campath-1H induction, half maintenance immunosuppression (Tacro, MMF) and no steroids; 40 received Thymoglobulin and 40 received Daclizumab for induction. The latter two groups received full dose of Tacro, MMF and steroids. CD4+ CD25+ brightly staining cells by flow cytometry were compared to pre-transplant and at monthly intervals post-transplantation to date in the three groups. These Treg (gated) cells were also tested for FoxP3 (by high speed sorting and real time PCR).
Results: A prolonged (p<0.001) increased frequency of Tregs was seen in the Campath-1H and Thymoglobulin groups at twice pre-transplant levels up to 240 days post-operability. With Daclizumab as induction the CD25 epitope was masked over the same period. In one patient tested, Tregs appeared to correlate with FoxP3 levels (real time PCR). This patient also received a similar Campath-1H protocol in addition to donor CD34+ stem cells. In this patient, Tregs have been three times the pre-Tx levels.
Conclusion: This simple quantification of Tregs by flow cytometry, might lead to a more optimum assessment of immune quiescence, allowing more exact monitoring of maintenance immunosuppression.