Bone marrow retaining colitogenic CD4+ T cells may be a pathogenic reservoir for chronic colitis

Gastroenterology. 2007 Jan;132(1):176-89. doi: 10.1053/j.gastro.2006.10.035. Epub 2006 Oct 25.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Bone Marrow Cells / immunology*
  • Bone Marrow Cells / metabolism
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / transplantation
  • Cell Division / immunology
  • Cell Survival / immunology
  • Chronic Disease
  • Colitis / drug therapy
  • Colitis / 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


  • 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