Bone Marrow Retaining Colitogenic CD4+ T Cells May Be a Pathogenic Reservoir for Chronic Colitis

Yasuhiro Nemoto, Takanori Kanai, Shin Makita, Ryuichi Okamoto, Teruji Totsuka, Kiyoshi Takeda, Mamoru Watanabe

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Background & Aims: Although bone marrow (BM) is known as a primary lymphoid organ, it also is known to harbor memory T cells, suggesting that this compartment is a preferential site for migration and/or selective retention of memory T cells. We here report the existence and the potential ability to induce colitis of the colitogenic BM CD4+ memory T cells in murine colitis models. Methods: We isolated BM CD4+ T cells obtained from colitic severe combined immunodeficient mice induced by the adoptive transfer of CD4+CD45RBhigh T cells and colitic interleukin (IL)-10-/- mice that develop colitis spontaneously, and analyzed the surface phenotype, cytokine production, and potential activity to induce colitis. Furthermore, we assessed the role of IL-7 to maintain the colitogenic BM CD4+ T cells. Results: A high number of CD4+ T cells reside in the BM of colitic severe combined immunodeficient mice and diseased IL-10-/- mice, and they retain significant potential to induce type-1 T helper-mediated colitis in an IL-7-dependent manner. These resident BM CD4+ T cells have an effector memory (TEM; CD44highCD62L-IL-7Rhigh) phenotype and preferentially are attached to IL-7-producing BM cells. Furthermore, the accumulation of BM CD4+ TEM cells was decreased significantly in IL-7-deficient recipients reconstituted with the colitogenic lamina propria CD4+ TEM cells. Conclusions: Collectively, these findings suggest that BM-retaining colitogenic CD4+ memory T cells in colitic mice play a critical role as a reservoir for persisting lifelong colitis.

Original languageEnglish
Pages (from-to)176-189
Number of pages14
JournalGastroenterology
Volume132
Issue number1
DOIs
Publication statusPublished - 2007 Jan
Externally publishedYes

Fingerprint

Colitis
Bone Marrow
T-Lymphocytes
Interleukin-7
SCID Mice
Interleukin-10
Phenotype
Aptitude
Adoptive Transfer
Interleukins
Bone Marrow Cells
Mucous Membrane
Cytokines

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Bone Marrow Retaining Colitogenic CD4+ T Cells May Be a Pathogenic Reservoir for Chronic Colitis. / Nemoto, Yasuhiro; Kanai, Takanori; Makita, Shin; Okamoto, Ryuichi; Totsuka, Teruji; Takeda, Kiyoshi; Watanabe, Mamoru.

In: Gastroenterology, Vol. 132, No. 1, 01.2007, p. 176-189.

Research output: Contribution to journalArticle

Nemoto, Y, Kanai, T, Makita, S, Okamoto, R, Totsuka, T, Takeda, K & Watanabe, M 2007, 'Bone Marrow Retaining Colitogenic CD4+ T Cells May Be a Pathogenic Reservoir for Chronic Colitis', Gastroenterology, vol. 132, no. 1, pp. 176-189. https://doi.org/10.1053/j.gastro.2006.10.035
Nemoto, Yasuhiro ; Kanai, Takanori ; Makita, Shin ; Okamoto, Ryuichi ; Totsuka, Teruji ; Takeda, Kiyoshi ; Watanabe, Mamoru. / Bone Marrow Retaining Colitogenic CD4+ T Cells May Be a Pathogenic Reservoir for Chronic Colitis. In: Gastroenterology. 2007 ; Vol. 132, No. 1. pp. 176-189.
@article{01db74075915490bbbf8b6ab646b1106,
title = "Bone Marrow Retaining Colitogenic CD4+ T Cells May Be a Pathogenic Reservoir for Chronic Colitis",
abstract = "Background & Aims: Although bone marrow (BM) is known as a primary lymphoid organ, it also is known to harbor memory T cells, suggesting that this compartment is a preferential site for migration and/or selective retention of memory T cells. We here report the existence and the potential ability to induce colitis of the colitogenic BM CD4+ memory T cells in murine colitis models. Methods: We isolated BM CD4+ T cells obtained from colitic severe combined immunodeficient mice induced by the adoptive transfer of CD4+CD45RBhigh T cells and colitic interleukin (IL)-10-/- mice that develop colitis spontaneously, and analyzed the surface phenotype, cytokine production, and potential activity to induce colitis. Furthermore, we assessed the role of IL-7 to maintain the colitogenic BM CD4+ T cells. Results: A high number of CD4+ T cells reside in the BM of colitic severe combined immunodeficient mice and diseased IL-10-/- mice, and they retain significant potential to induce type-1 T helper-mediated colitis in an IL-7-dependent manner. These resident BM CD4+ T cells have an effector memory (TEM; CD44highCD62L-IL-7Rhigh) phenotype and preferentially are attached to IL-7-producing BM cells. Furthermore, the accumulation of BM CD4+ TEM cells was decreased significantly in IL-7-deficient recipients reconstituted with the colitogenic lamina propria CD4+ TEM cells. Conclusions: Collectively, these findings suggest that BM-retaining colitogenic CD4+ memory T cells in colitic mice play a critical role as a reservoir for persisting lifelong colitis.",
author = "Yasuhiro Nemoto and Takanori Kanai and Shin Makita and Ryuichi Okamoto and Teruji Totsuka and Kiyoshi Takeda and Mamoru Watanabe",
year = "2007",
month = "1",
doi = "10.1053/j.gastro.2006.10.035",
language = "English",
volume = "132",
pages = "176--189",
journal = "Gastroenterology",
issn = "0016-5085",
publisher = "W.B. Saunders Ltd",
number = "1",

}

TY - JOUR

T1 - Bone Marrow Retaining Colitogenic CD4+ T Cells May Be a Pathogenic Reservoir for Chronic Colitis

AU - Nemoto, Yasuhiro

AU - Kanai, Takanori

AU - Makita, Shin

AU - Okamoto, Ryuichi

AU - Totsuka, Teruji

AU - Takeda, Kiyoshi

AU - Watanabe, Mamoru

PY - 2007/1

Y1 - 2007/1

N2 - Background & Aims: Although bone marrow (BM) is known as a primary lymphoid organ, it also is known to harbor memory T cells, suggesting that this compartment is a preferential site for migration and/or selective retention of memory T cells. We here report the existence and the potential ability to induce colitis of the colitogenic BM CD4+ memory T cells in murine colitis models. Methods: We isolated BM CD4+ T cells obtained from colitic severe combined immunodeficient mice induced by the adoptive transfer of CD4+CD45RBhigh T cells and colitic interleukin (IL)-10-/- mice that develop colitis spontaneously, and analyzed the surface phenotype, cytokine production, and potential activity to induce colitis. Furthermore, we assessed the role of IL-7 to maintain the colitogenic BM CD4+ T cells. Results: A high number of CD4+ T cells reside in the BM of colitic severe combined immunodeficient mice and diseased IL-10-/- mice, and they retain significant potential to induce type-1 T helper-mediated colitis in an IL-7-dependent manner. These resident BM CD4+ T cells have an effector memory (TEM; CD44highCD62L-IL-7Rhigh) phenotype and preferentially are attached to IL-7-producing BM cells. Furthermore, the accumulation of BM CD4+ TEM cells was decreased significantly in IL-7-deficient recipients reconstituted with the colitogenic lamina propria CD4+ TEM cells. Conclusions: Collectively, these findings suggest that BM-retaining colitogenic CD4+ memory T cells in colitic mice play a critical role as a reservoir for persisting lifelong colitis.

AB - Background & Aims: Although bone marrow (BM) is known as a primary lymphoid organ, it also is known to harbor memory T cells, suggesting that this compartment is a preferential site for migration and/or selective retention of memory T cells. We here report the existence and the potential ability to induce colitis of the colitogenic BM CD4+ memory T cells in murine colitis models. Methods: We isolated BM CD4+ T cells obtained from colitic severe combined immunodeficient mice induced by the adoptive transfer of CD4+CD45RBhigh T cells and colitic interleukin (IL)-10-/- mice that develop colitis spontaneously, and analyzed the surface phenotype, cytokine production, and potential activity to induce colitis. Furthermore, we assessed the role of IL-7 to maintain the colitogenic BM CD4+ T cells. Results: A high number of CD4+ T cells reside in the BM of colitic severe combined immunodeficient mice and diseased IL-10-/- mice, and they retain significant potential to induce type-1 T helper-mediated colitis in an IL-7-dependent manner. These resident BM CD4+ T cells have an effector memory (TEM; CD44highCD62L-IL-7Rhigh) phenotype and preferentially are attached to IL-7-producing BM cells. Furthermore, the accumulation of BM CD4+ TEM cells was decreased significantly in IL-7-deficient recipients reconstituted with the colitogenic lamina propria CD4+ TEM cells. Conclusions: Collectively, these findings suggest that BM-retaining colitogenic CD4+ memory T cells in colitic mice play a critical role as a reservoir for persisting lifelong colitis.

UR - http://www.scopus.com/inward/record.url?scp=33846214034&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846214034&partnerID=8YFLogxK

U2 - 10.1053/j.gastro.2006.10.035

DO - 10.1053/j.gastro.2006.10.035

M3 - Article

VL - 132

SP - 176

EP - 189

JO - Gastroenterology

JF - Gastroenterology

SN - 0016-5085

IS - 1

ER -