Expansion of a restricted residual host Treg‐cell repertoire is dependent on IL‐2 following experimental autologous hematopoietic stem transplantation

We previously identified a population of residual Treg cells following autologous hematopoietic stem transplantation (HSCT), that rapidly undergoes significant expansion in lymphopenic transplant recipients prior to repopulation by donor de novo derived Treg cells. These CD4+Foxp3+ T cells provide p...

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Bibliographic Details
Published in:European journal of immunology 2011-12, Vol.41 (12), p.3467-3478
Main Authors: Bayer, Allison L., Chirinos, Jackeline, Cabello, Cecilia, Yang, Jing, Matsutani, Takaji, Malek, Thomas R., Levy, Robert B.
Format: Article
Language:English
Subjects:
Autoimmune diseases
CD4+ T cells
Cytokines
Expansion
T cell receptors
T regulatory cell
Transplantation
Transplants & implants
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Summary:We previously identified a population of residual Treg cells following autologous hematopoietic stem transplantation (HSCT), that rapidly undergoes significant expansion in lymphopenic transplant recipients prior to repopulation by donor de novo derived Treg cells. These CD4+Foxp3+ T cells provide protection from the development of autoimmune disease. Although ablative conditioning results in excess IL‐7 and IL‐15, IL‐2 is typically not found at high levels following autologous HSCT. We therefore examined the role of these three STAT‐5 signaling cytokines in the expansion of residual Treg cells after autologous HSCT. The present study found that the residual Treg cell population included surviving peripheral host Foxp3+CD4+ T cells whose expansion was critically dependent on IL‐2, which could be solely provided by surviving host cells. IL‐7 was found to contribute to Treg cell homeostasis, however, not as a growth factor but rather for their persistence. In conjunction with this expansion, TCR spectratype analyses revealed that the residual host Treg‐cell compartment differed from that present in non‐conditioned healthy mice since the residual host Treg cells exhibit a limited TCR diversity. Collectively, these data indicate that the proliferation of Treg and T effector (Teff) cells post‐HSCT utilize separate pools of cytokines which has important implications regarding the development of clinical strategies to elicit the desired immune responses in patients post‐transplant.
ISSN:0014-2980
1521-4141
DOI:10.1002/eji.201141611