Am J Transplant, Vol 8, pp 793-802, 2008
CD4+CD25+FOXP3+ Regulatory T Cells Increase De Novo in Kidney Transplant Patients After Immunodepletion with Campath-1H
Bloom DD, et al
Campath-1H (Alemtuzumab) is an effective immunodepletion agent used
in renal transplantation. To evaluate its influence on T lymphocytes
during repletion, we analyzed peripheral blood from Campath-1H-treated
renal allograft recipients for the presence of FOXP3+ regulatory T (Treg) cells. Flow cytometry demonstrated that CD4+CD25+FOXP3+ lymphocytes increased significantly within the CD4+
T-cell population, skewing Treg/Teff (T effector) ratios for up to
several years. In contrast, Treg levels in patients treated with
anti-CD25 (Basiliximab) and maintained on CsA demonstrated a sustained
decrease. The increase in Tregs in Campath-1H treated patients
developed independent of maintenance immunosuppression. Importantly,
the increase in Tregs was not fully explained by their homeostatic
proliferation, increased thymic output, or Treg sparing, suggesting de novo generation/expansion. Consistent with this, in vitro stimulation of PBMCs with Campath-1H, with or without anti-CD3, activation led to an increase in CD4+CD25+FOXP3+
cells that had suppressive capabilities. Together, these data suggest
that Campath-1H promotes an increase in peripheral Tregs and may act as
an intrinsic generator of Tregs in vivo.
