Induction of regulatory T cells from mature T cells by allogeneic thymic epithelial cells in vitro

Yimin Sun, Bao Sheng Ge, Michiyuki Kasai, Clara Diffendaffer, Nancy Parks, Hanhan Li, Jianxia Peng, Alan Norman Langnas, Yong Zhao

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The ability of thymic epithelial cells (TEC) to re-educate mature T cells to be regulatory T cells has not been addressed. In the present study, this issue was directly investigated by co-culturing of mature T cells and allo-TECs. B6 macrophage cell line 1C21-cultured BALB/c splenocytes responded to B6 antigens in vitro. However, BALB/c splenocytes precultured with B6-derived TECs 1-4C18 or 1C6 did not proliferate to B6 antigens, but responded to rat antigens. Exogenous interleukin-2 (IL-2)q2 failed to revise the unresponsiveness of these T cells. Allo-TEC-cultured T cells predominantly expressed Th2 cytokines (IL-4 and IL-10). B6 TEC-cultured BALB/c splenocytes markedly inhibited the immune responses of naïve BALB/c splenocytes to B6 antigens, but not to rat or the third-party mouse antigens. BALB/c nude mice that received naïve syngeneic splenocytes rejected B6 or rat skin grafts by 17 days postskin grafting; however, co-injection of B6 TEC-cultured BALB/c splenocytes significantly delayed B6 skin graft rejection (P < 0.01), with the unchanged rejection of rat skin grafts. These studies demonstrate that allo-TECs are able to 'educate' mature T cells to be regulatory cells, and suggest that regulatory cells derived from mature T cells by TECs may play an important role in T cell tolerance to allo- and auto-antigens.

Original languageEnglish (US)
Pages (from-to)404-414
Number of pages11
JournalTransplant International
Volume19
Issue number5
DOIs
StatePublished - May 1 2006

Fingerprint

Regulatory T-Lymphocytes
Epithelial Cells
T-Lymphocytes
Antigens
Skin
Transplants
Graft Rejection
In Vitro Techniques
Nude Mice
Interleukin-4
Interleukin-10
Interleukin-2
Cultured Cells
Macrophages
Cytokines
Cell Line
Injections

Keywords

  • Epithelial cells
  • Regulatory T cells (Treg)
  • T cells
  • Thymus
  • Transplantation

ASJC Scopus subject areas

  • Transplantation

Cite this

Induction of regulatory T cells from mature T cells by allogeneic thymic epithelial cells in vitro. / Sun, Yimin; Ge, Bao Sheng; Kasai, Michiyuki; Diffendaffer, Clara; Parks, Nancy; Li, Hanhan; Peng, Jianxia; Langnas, Alan Norman; Zhao, Yong.

In: Transplant International, Vol. 19, No. 5, 01.05.2006, p. 404-414.

Research output: Contribution to journalArticle

Sun, Yimin ; Ge, Bao Sheng ; Kasai, Michiyuki ; Diffendaffer, Clara ; Parks, Nancy ; Li, Hanhan ; Peng, Jianxia ; Langnas, Alan Norman ; Zhao, Yong. / Induction of regulatory T cells from mature T cells by allogeneic thymic epithelial cells in vitro. In: Transplant International. 2006 ; Vol. 19, No. 5. pp. 404-414.
@article{8af44da4bb5448239f95c7e7337aa453,
title = "Induction of regulatory T cells from mature T cells by allogeneic thymic epithelial cells in vitro",
abstract = "The ability of thymic epithelial cells (TEC) to re-educate mature T cells to be regulatory T cells has not been addressed. In the present study, this issue was directly investigated by co-culturing of mature T cells and allo-TECs. B6 macrophage cell line 1C21-cultured BALB/c splenocytes responded to B6 antigens in vitro. However, BALB/c splenocytes precultured with B6-derived TECs 1-4C18 or 1C6 did not proliferate to B6 antigens, but responded to rat antigens. Exogenous interleukin-2 (IL-2)q2 failed to revise the unresponsiveness of these T cells. Allo-TEC-cultured T cells predominantly expressed Th2 cytokines (IL-4 and IL-10). B6 TEC-cultured BALB/c splenocytes markedly inhibited the immune responses of na{\"i}ve BALB/c splenocytes to B6 antigens, but not to rat or the third-party mouse antigens. BALB/c nude mice that received na{\"i}ve syngeneic splenocytes rejected B6 or rat skin grafts by 17 days postskin grafting; however, co-injection of B6 TEC-cultured BALB/c splenocytes significantly delayed B6 skin graft rejection (P < 0.01), with the unchanged rejection of rat skin grafts. These studies demonstrate that allo-TECs are able to 'educate' mature T cells to be regulatory cells, and suggest that regulatory cells derived from mature T cells by TECs may play an important role in T cell tolerance to allo- and auto-antigens.",
keywords = "Epithelial cells, Regulatory T cells (Treg), T cells, Thymus, Transplantation",
author = "Yimin Sun and Ge, {Bao Sheng} and Michiyuki Kasai and Clara Diffendaffer and Nancy Parks and Hanhan Li and Jianxia Peng and Langnas, {Alan Norman} and Yong Zhao",
year = "2006",
month = "5",
day = "1",
doi = "10.1111/j.1432-2277.2006.00300.x",
language = "English (US)",
volume = "19",
pages = "404--414",
journal = "Transplant International",
issn = "0934-0874",
publisher = "Wiley-Blackwell",
number = "5",

}

TY - JOUR

T1 - Induction of regulatory T cells from mature T cells by allogeneic thymic epithelial cells in vitro

AU - Sun, Yimin

AU - Ge, Bao Sheng

AU - Kasai, Michiyuki

AU - Diffendaffer, Clara

AU - Parks, Nancy

AU - Li, Hanhan

AU - Peng, Jianxia

AU - Langnas, Alan Norman

AU - Zhao, Yong

PY - 2006/5/1

Y1 - 2006/5/1

N2 - The ability of thymic epithelial cells (TEC) to re-educate mature T cells to be regulatory T cells has not been addressed. In the present study, this issue was directly investigated by co-culturing of mature T cells and allo-TECs. B6 macrophage cell line 1C21-cultured BALB/c splenocytes responded to B6 antigens in vitro. However, BALB/c splenocytes precultured with B6-derived TECs 1-4C18 or 1C6 did not proliferate to B6 antigens, but responded to rat antigens. Exogenous interleukin-2 (IL-2)q2 failed to revise the unresponsiveness of these T cells. Allo-TEC-cultured T cells predominantly expressed Th2 cytokines (IL-4 and IL-10). B6 TEC-cultured BALB/c splenocytes markedly inhibited the immune responses of naïve BALB/c splenocytes to B6 antigens, but not to rat or the third-party mouse antigens. BALB/c nude mice that received naïve syngeneic splenocytes rejected B6 or rat skin grafts by 17 days postskin grafting; however, co-injection of B6 TEC-cultured BALB/c splenocytes significantly delayed B6 skin graft rejection (P < 0.01), with the unchanged rejection of rat skin grafts. These studies demonstrate that allo-TECs are able to 'educate' mature T cells to be regulatory cells, and suggest that regulatory cells derived from mature T cells by TECs may play an important role in T cell tolerance to allo- and auto-antigens.

AB - The ability of thymic epithelial cells (TEC) to re-educate mature T cells to be regulatory T cells has not been addressed. In the present study, this issue was directly investigated by co-culturing of mature T cells and allo-TECs. B6 macrophage cell line 1C21-cultured BALB/c splenocytes responded to B6 antigens in vitro. However, BALB/c splenocytes precultured with B6-derived TECs 1-4C18 or 1C6 did not proliferate to B6 antigens, but responded to rat antigens. Exogenous interleukin-2 (IL-2)q2 failed to revise the unresponsiveness of these T cells. Allo-TEC-cultured T cells predominantly expressed Th2 cytokines (IL-4 and IL-10). B6 TEC-cultured BALB/c splenocytes markedly inhibited the immune responses of naïve BALB/c splenocytes to B6 antigens, but not to rat or the third-party mouse antigens. BALB/c nude mice that received naïve syngeneic splenocytes rejected B6 or rat skin grafts by 17 days postskin grafting; however, co-injection of B6 TEC-cultured BALB/c splenocytes significantly delayed B6 skin graft rejection (P < 0.01), with the unchanged rejection of rat skin grafts. These studies demonstrate that allo-TECs are able to 'educate' mature T cells to be regulatory cells, and suggest that regulatory cells derived from mature T cells by TECs may play an important role in T cell tolerance to allo- and auto-antigens.

KW - Epithelial cells

KW - Regulatory T cells (Treg)

KW - T cells

KW - Thymus

KW - Transplantation

UR - http://www.scopus.com/inward/record.url?scp=33646013906&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33646013906&partnerID=8YFLogxK

U2 - 10.1111/j.1432-2277.2006.00300.x

DO - 10.1111/j.1432-2277.2006.00300.x

M3 - Article

C2 - 16623876

AN - SCOPUS:33646013906

VL - 19

SP - 404

EP - 414

JO - Transplant International

JF - Transplant International

SN - 0934-0874

IS - 5

ER -