Expansion of a restricted residual host T reg-cell repertoire is dependent on IL-2 following experimental autologous hematopoietic stem transplantation

Allison L. Bayer, Jackeline Chirinos, Cecilia Cabello, Jing Yang, Takaji Matsutani, Thomas R. Malek, Robert B. Levy

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

We previously identified a population of residual T reg cells following autologous hematopoietic stem transplantation (HSCT), that rapidly undergoes significant expansion in lymphopenic transplant recipients prior to repopulation by donor de novo derived T reg 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 T reg cells after autologous HSCT. The present study found that the residual T reg 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 T reg 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 T reg-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 T reg and T effector (T eff) 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.

Original languageEnglish (US)
Pages (from-to)3467-3478
Number of pages12
JournalEuropean Journal of Immunology
Volume41
Issue number12
DOIs
StatePublished - Dec 2011

Keywords

  • BM
  • CD4 T cells
  • Cytokines
  • T regulatory cell
  • Transplantation

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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