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+ CD45RB(high) 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 (T(EM); CD44(high)CD62L(-)IL-7R(high)) phenotype and preferentially are attached to IL-7-producing BM cells. Furthermore, the accumulation of BM CD4+ T(EM) cells was decreased significantly in IL-7-deficient recipients reconstituted with the colitogenic lamina propria CD4+ T(EM) 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.

• Authors: Yasuhiro Nemoto, Takanori Kanai, Shin Makita, Ryuichi Okamoto, Teruji Totsuka, Kiyoshi Takeda, Mamoru Watanabe
• Journal: Gastroenterology (Gastroenterology) Vol. 132 Issue 1 Pg. 176-89 (Jan 2007) ISSN: 0016-5085 [Print] United States
• PMID: 17241870 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• DNA-Binding Proteins
• Interleukin-2
• Interleukin-7
• Rag2 protein, mouse
• Tumor Necrosis Factor-alpha
• Interleukin-10
• Interferon-gamma
• Leukocyte Common Antigens
• Protein Tyrosine Phosphatase, Non-Receptor Type 1

Topics

• Adoptive Transfer
• Animals
• Anti-Bacterial Agents (pharmacology)
• Bone Marrow Cells (immunology, metabolism)
• CD4-Positive T-Lymphocytes (immunology, metabolism, transplantation)
• Cell Division (immunology)
• Cell Survival (immunology)
• Chronic Disease
• Colitis (drug therapy, immunology)
• Colon (immunology)
• DNA-Binding Proteins (genetics)
• Female
• Homeostasis (immunology)
• Immunologic Memory
• Interferon-gamma (metabolism)
• Interleukin-10 (genetics)
• Interleukin-2 (metabolism)
• Interleukin-7 (metabolism)
• Leukocyte Common Antigens (metabolism)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Mutant Strains
• Mice, SCID
• Protein Tyrosine Phosphatase, Non-Receptor Type 1
• Tumor Necrosis Factor-alpha (metabolism)