Submitted August 12, 2008
Accepted September 10, 2008
Host CD4+CD25+ T cells can expand and comprise a major component of the Treg compartment following experimental HCT
Allison L Bayer, Monica Jones, Jackeline Chirinos, Lesley de Armas, Taylor H Schreiber, Thomas R. Malek, and Robert B Levy*
Department of Microbiology/Immunology, University of Miami Miller School of Medicine, Miami, FL, United States
Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, United States
* Corresponding author; email: rlevy{at}med.miami.edu.
Reconstitution of the recipient lymphoid compartment following hematopoietic cell transplantation (HCT) is typically delayed. The present studies investigated the residual host CD4+CD25+Foxp3+ (Treg) compartment following several conditioning regimens including T cell depleted (TCD) and replete (TCR) HCT and observed: 1) a small number of recipient Treg cells survived aggressive conditioning, 2) the surviving, i.e. residual Tregs underwent marked expansion and 3) recipient CD4+FoxP3+ cells comprised the majority of the Treg compartment for several months post-syngeneic HCT. Notably, residual Tregs also dominated the compartment following HCT with TCD MHC-matched allogeneic bone marrow (BM) but not following TCR transplants. The residual Treg cell compartment was functionally competent as assessed by in vitro lymphoid suppression and in vivo autoimmune disease transfer assay. These observations support the notion that functional host Tregs initially occupy a niche in lymphopenic transplant recipients, undergo significant expansion and contribute to the compartment for an extended period before donor derived CD4+FoxP3+ T cells eventually comprise the majority of the compartment. In total, the findings suggest that the presence of host Tregs may be important to consider regarding elicitation of immune (ex. anti-tumor, vaccine) responses in recipients during the early post-transplant period involving autologous and certain allogeneic HCT regimens.
