Differential expression of Smad7 transcripts identifies the CD4+CD45RChigh regulatory T cells that mediate type V collagen-induced tolerance to lung allografts

Teruaki Mizobuchi, Kazuhiro Yasufuku, Yan Zheng, M. Azizul Haque, Kathleen M. Heidler, Kena Woods, Gerald N. Smith, Oscar Cummings, Takehiko Fujisawa, Janice Blum, David S. Wilkes

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Regulatory T cells (Tregs) induced by oral tolerance may suppress immunity by production of TGF-β that could also enhance Treg activity. However, all cells that are phenotypically Tregs in rats (CD4+CD45RChigh-RChigh) may not have regulatory function. Because Smad7 expression in T cells is associated with inflammation and autoimmunity, then lack of Smad7 may identify those cells that function as Tregs. We reported that feeding type V collagen (col(V)) to WKY rats (RT11) induces oral tolerance to lung allografts (F344-RT11v1) by T cells that produce TGF-β. The purpose of the current study was to identify the Tregs that mediate col(V)-induced tolerance, and determine Smad7 expression in these cells. RChigh cells from tolerant rats were unresponsive to allogeneic stimulation and abrogated rejection after adoptive transfer. In contrast, CD4+CD45RClow (RClow) cells from tolerant rats and RChigh or RClow cells from normal rats or untreated allograft recipients proliferated vigorously in response to donor Ags, and did not suppress rejection after adoptive transfer. TGF-β enhanced proliferation in response to col(V) presented to tolerant RChigh, but not other cells. In contrast to other cells, only RChigh cells from tolerant rats did not express Smad7. Collectively, these data show that the Tregs that mediate col(V)-induced tolerance to lung allografts do not express SMAD7 and, therefore, are permissive to TGF-β-mediated signaling.

Original languageEnglish
Pages (from-to)1140-1147
Number of pages8
JournalJournal of Immunology
Volume171
Issue number3
StatePublished - Aug 1 2003

Fingerprint

Collagen Type V
Regulatory T-Lymphocytes
Allografts
Lung
Adoptive Transfer
T-Lymphocytes
Inbred WKY Rats
Autoimmunity
Immunity
Inflammation

ASJC Scopus subject areas

  • Immunology

Cite this

Mizobuchi, T., Yasufuku, K., Zheng, Y., Haque, M. A., Heidler, K. M., Woods, K., ... Wilkes, D. S. (2003). Differential expression of Smad7 transcripts identifies the CD4+CD45RChigh regulatory T cells that mediate type V collagen-induced tolerance to lung allografts. Journal of Immunology, 171(3), 1140-1147.

Differential expression of Smad7 transcripts identifies the CD4+CD45RChigh regulatory T cells that mediate type V collagen-induced tolerance to lung allografts. / Mizobuchi, Teruaki; Yasufuku, Kazuhiro; Zheng, Yan; Haque, M. Azizul; Heidler, Kathleen M.; Woods, Kena; Smith, Gerald N.; Cummings, Oscar; Fujisawa, Takehiko; Blum, Janice; Wilkes, David S.

In: Journal of Immunology, Vol. 171, No. 3, 01.08.2003, p. 1140-1147.

Research output: Contribution to journalArticle

Mizobuchi, T, Yasufuku, K, Zheng, Y, Haque, MA, Heidler, KM, Woods, K, Smith, GN, Cummings, O, Fujisawa, T, Blum, J & Wilkes, DS 2003, 'Differential expression of Smad7 transcripts identifies the CD4+CD45RChigh regulatory T cells that mediate type V collagen-induced tolerance to lung allografts', Journal of Immunology, vol. 171, no. 3, pp. 1140-1147.
Mizobuchi, Teruaki ; Yasufuku, Kazuhiro ; Zheng, Yan ; Haque, M. Azizul ; Heidler, Kathleen M. ; Woods, Kena ; Smith, Gerald N. ; Cummings, Oscar ; Fujisawa, Takehiko ; Blum, Janice ; Wilkes, David S. / Differential expression of Smad7 transcripts identifies the CD4+CD45RChigh regulatory T cells that mediate type V collagen-induced tolerance to lung allografts. In: Journal of Immunology. 2003 ; Vol. 171, No. 3. pp. 1140-1147.
@article{c2906891a6bc463fa53b9e8e681d4ad2,
title = "Differential expression of Smad7 transcripts identifies the CD4+CD45RChigh regulatory T cells that mediate type V collagen-induced tolerance to lung allografts",
abstract = "Regulatory T cells (Tregs) induced by oral tolerance may suppress immunity by production of TGF-β that could also enhance Treg activity. However, all cells that are phenotypically Tregs in rats (CD4+CD45RChigh-RChigh) may not have regulatory function. Because Smad7 expression in T cells is associated with inflammation and autoimmunity, then lack of Smad7 may identify those cells that function as Tregs. We reported that feeding type V collagen (col(V)) to WKY rats (RT11) induces oral tolerance to lung allografts (F344-RT11v1) by T cells that produce TGF-β. The purpose of the current study was to identify the Tregs that mediate col(V)-induced tolerance, and determine Smad7 expression in these cells. RChigh cells from tolerant rats were unresponsive to allogeneic stimulation and abrogated rejection after adoptive transfer. In contrast, CD4+CD45RClow (RClow) cells from tolerant rats and RChigh or RClow cells from normal rats or untreated allograft recipients proliferated vigorously in response to donor Ags, and did not suppress rejection after adoptive transfer. TGF-β enhanced proliferation in response to col(V) presented to tolerant RChigh, but not other cells. In contrast to other cells, only RChigh cells from tolerant rats did not express Smad7. Collectively, these data show that the Tregs that mediate col(V)-induced tolerance to lung allografts do not express SMAD7 and, therefore, are permissive to TGF-β-mediated signaling.",
author = "Teruaki Mizobuchi and Kazuhiro Yasufuku and Yan Zheng and Haque, {M. Azizul} and Heidler, {Kathleen M.} and Kena Woods and Smith, {Gerald N.} and Oscar Cummings and Takehiko Fujisawa and Janice Blum and Wilkes, {David S.}",
year = "2003",
month = "8",
day = "1",
language = "English",
volume = "171",
pages = "1140--1147",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "3",

}

TY - JOUR

T1 - Differential expression of Smad7 transcripts identifies the CD4+CD45RChigh regulatory T cells that mediate type V collagen-induced tolerance to lung allografts

AU - Mizobuchi, Teruaki

AU - Yasufuku, Kazuhiro

AU - Zheng, Yan

AU - Haque, M. Azizul

AU - Heidler, Kathleen M.

AU - Woods, Kena

AU - Smith, Gerald N.

AU - Cummings, Oscar

AU - Fujisawa, Takehiko

AU - Blum, Janice

AU - Wilkes, David S.

PY - 2003/8/1

Y1 - 2003/8/1

N2 - Regulatory T cells (Tregs) induced by oral tolerance may suppress immunity by production of TGF-β that could also enhance Treg activity. However, all cells that are phenotypically Tregs in rats (CD4+CD45RChigh-RChigh) may not have regulatory function. Because Smad7 expression in T cells is associated with inflammation and autoimmunity, then lack of Smad7 may identify those cells that function as Tregs. We reported that feeding type V collagen (col(V)) to WKY rats (RT11) induces oral tolerance to lung allografts (F344-RT11v1) by T cells that produce TGF-β. The purpose of the current study was to identify the Tregs that mediate col(V)-induced tolerance, and determine Smad7 expression in these cells. RChigh cells from tolerant rats were unresponsive to allogeneic stimulation and abrogated rejection after adoptive transfer. In contrast, CD4+CD45RClow (RClow) cells from tolerant rats and RChigh or RClow cells from normal rats or untreated allograft recipients proliferated vigorously in response to donor Ags, and did not suppress rejection after adoptive transfer. TGF-β enhanced proliferation in response to col(V) presented to tolerant RChigh, but not other cells. In contrast to other cells, only RChigh cells from tolerant rats did not express Smad7. Collectively, these data show that the Tregs that mediate col(V)-induced tolerance to lung allografts do not express SMAD7 and, therefore, are permissive to TGF-β-mediated signaling.

AB - Regulatory T cells (Tregs) induced by oral tolerance may suppress immunity by production of TGF-β that could also enhance Treg activity. However, all cells that are phenotypically Tregs in rats (CD4+CD45RChigh-RChigh) may not have regulatory function. Because Smad7 expression in T cells is associated with inflammation and autoimmunity, then lack of Smad7 may identify those cells that function as Tregs. We reported that feeding type V collagen (col(V)) to WKY rats (RT11) induces oral tolerance to lung allografts (F344-RT11v1) by T cells that produce TGF-β. The purpose of the current study was to identify the Tregs that mediate col(V)-induced tolerance, and determine Smad7 expression in these cells. RChigh cells from tolerant rats were unresponsive to allogeneic stimulation and abrogated rejection after adoptive transfer. In contrast, CD4+CD45RClow (RClow) cells from tolerant rats and RChigh or RClow cells from normal rats or untreated allograft recipients proliferated vigorously in response to donor Ags, and did not suppress rejection after adoptive transfer. TGF-β enhanced proliferation in response to col(V) presented to tolerant RChigh, but not other cells. In contrast to other cells, only RChigh cells from tolerant rats did not express Smad7. Collectively, these data show that the Tregs that mediate col(V)-induced tolerance to lung allografts do not express SMAD7 and, therefore, are permissive to TGF-β-mediated signaling.

UR - http://www.scopus.com/inward/record.url?scp=0041845185&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0041845185&partnerID=8YFLogxK

M3 - Article

C2 - 12874199

AN - SCOPUS:0041845185

VL - 171

SP - 1140

EP - 1147

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 3

ER -