Journal article
T helper cell 1-type CD4+ T cells, but not B cells, mediate colitis in interleukin 10-deficient mice
The Journal of experimental medicine, Vol.184(1), pp.241-251
07/01/1996
DOI: 10.1084/jem.184.1.241
PMCID: PMC2192682
PMID: 8691138
Abstract
Mice rendered deficient in the production of interleukin 10 (IL-10-/-) develop a chronic inflammatory bowel disease (IBD) that predominates in the colon and shares histopathological features with human IBD. Our aim was to identify which cell type(s) can mediate colitis in IL-10-/- mice. We detected an influx of immunoglobulin-positive cells into the colon and the presence of colon-reactive antibodies in the serum of IL-10-/- mice. To assess a pathogenic role for B cells, we generated a B cell-deficient (B-/-) strain of IL-10-/- mice. B-/-IL-10-/- mice acquired a severe colitis analogous to that IL-10-/- mice, implying that B cells were not the primary mediator of IBD in this model. A series of cell transfer experiments was performed to assess a pathogenic role for T cells. When IL-10-/- T cell-enriched lamina propria lymphocytes (LPL) or intraepithelial lymphocytes (IEL) were transferred into immunodeficient recombinase-activating gene (RAG)-2-/- recipients, a mild to severe colitis developed, depending on the cell number transferred. Lymphocytes recovered from the colon of transplanted RAG-2-/- mice with colitis were predominantly alpha beta TCR+CD4+, including a large proportion of CD4+CD8 alpha + cells. These cells were also CD45RB-/low and CD44+, indicative of an activated/memory population. Individual populations of CD4+CD8 alpha-, CD4+CD8 alpha + and CD4-CD8 alpha + T cells were then isolated from the lamina propria compartment of IL-10-/- mice and transferred into RAG-2-/- recipients. Only IL-10-/- CD4-expressing LPL, including both the CD4+CD8 alpha- and CD4+CD8 alpha + populations, induced colitis in recipient mice. Interferon-gamma, but little to no IL-4, was produced by CD4+CD8 alpha- and CD4+CD8 alpha + LPL recovered from the inflamed colons of RAG-2-/- recipients implicating alpha T helper cell 1 (TH1)-mediated response. We thus conclude that colitis in IL-10-/- mice is predominantly mediated by TH1-type alpha beta TCR+ T cells expressing CD4 alone, or in combination with the CD8 alpha molecule.
Details
- Title: Subtitle
- T helper cell 1-type CD4+ T cells, but not B cells, mediate colitis in interleukin 10-deficient mice
- Creators
- Natalie J Davidson - DNAX Research Institute of Molecular and Cellular Biology Inc., Palo Alto, California 94304, USAMichael W Leach - DNAX Research Institute of Molecular and Cellular Biology Inc., Palo Alto, California 94304, USAMadeline M Fort - DNAX Research Institute of Molecular and Cellular Biology Inc., Palo Alto, California 94304, USALuAnn Thompson-Snipes - DNAX Research Institute of Molecular and Cellular Biology Inc., Palo Alto, California 94304, USARalf Kühn - DNAX Research Institute of Molecular and Cellular Biology Inc., Palo Alto, California 94304, USAWerner Müller - DNAX Research Institute of Molecular and Cellular Biology Inc., Palo Alto, California 94304, USADaniel J Berg - DNAX Research Institute of Molecular and Cellular Biology Inc., Palo Alto, California 94304, USADonna M Rennick - DNAX Research Institute of Molecular and Cellular Biology Inc., Palo Alto, California 94304, USA
- Resource Type
- Journal article
- Publication Details
- The Journal of experimental medicine, Vol.184(1), pp.241-251
- DOI
- 10.1084/jem.184.1.241
- PMID
- 8691138
- PMCID
- PMC2192682
- ISSN
- 0022-1007
- eISSN
- 1540-9538
- Language
- English
- Date published
- 07/01/1996
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984094381802771
Metrics
11 Record Views