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 Malek, Robert B Levy

Research output: Contribution to journalArticle

7 Citations (Scopus)

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
Pages (from-to)3467-3478
Number of pages12
JournalEuropean Journal of Immunology
Volume41
Issue number12
DOIs
StatePublished - Dec 1 2011

Fingerprint

Interleukin-2
Transplantation
Interleukin-7
Cytokines
T-Lymphocytes
Interleukin-15
Cytoprotection
Regulatory T-Lymphocytes
Population
Autoimmune Diseases
Intercellular Signaling Peptides and Proteins
Homeostasis
Tissue Donors
Transplants

Keywords

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

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Expansion of a restricted residual host T reg-cell repertoire is dependent on IL-2 following experimental autologous hematopoietic stem transplantation. / Bayer, Allison L; Chirinos, Jackeline; Cabello, Cecilia; Yang, Jing; Matsutani, Takaji; Malek, Thomas; Levy, Robert B.

In: European Journal of Immunology, Vol. 41, No. 12, 01.12.2011, p. 3467-3478.

Research output: Contribution to journalArticle

@article{40e997b68450487e818ef1f786dac430,
title = "Expansion of a restricted residual host T reg-cell repertoire is dependent on IL-2 following experimental autologous hematopoietic stem transplantation",
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.",
keywords = "BM, CD4 T cells, Cytokines, T regulatory cell, Transplantation",
author = "Bayer, {Allison L} and Jackeline Chirinos and Cecilia Cabello and Jing Yang and Takaji Matsutani and Thomas Malek and Levy, {Robert B}",
year = "2011",
month = "12",
day = "1",
doi = "10.1002/eji.201141611",
language = "English",
volume = "41",
pages = "3467--3478",
journal = "European Journal of Immunology",
issn = "0014-2980",
publisher = "Wiley-VCH Verlag",
number = "12",

}

TY - JOUR

T1 - Expansion of a restricted residual host T reg-cell repertoire is dependent on IL-2 following experimental autologous hematopoietic stem transplantation

AU - Bayer, Allison L

AU - Chirinos, Jackeline

AU - Cabello, Cecilia

AU - Yang, Jing

AU - Matsutani, Takaji

AU - Malek, Thomas

AU - Levy, Robert B

PY - 2011/12/1

Y1 - 2011/12/1

N2 - 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.

AB - 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.

KW - BM

KW - CD4 T cells

KW - Cytokines

KW - T regulatory cell

KW - Transplantation

UR - http://www.scopus.com/inward/record.url?scp=82255194212&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=82255194212&partnerID=8YFLogxK

U2 - 10.1002/eji.201141611

DO - 10.1002/eji.201141611

M3 - Article

C2 - 21928285

AN - SCOPUS:82255194212

VL - 41

SP - 3467

EP - 3478

JO - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

IS - 12

ER -