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T helper cell 1-type CD4+ T cells, but not B cells, mediate colitis in interleukin 10-deficient mice

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Item Type:Article
Title:T helper cell 1-type CD4+ T cells, but not B cells, mediate colitis in interleukin 10-deficient mice
Creators Name:Davidson, N.J. and Leach, M.W. and Fort, M.M. and Thompson-Snipes, L. and Kuehn, R. and Mueller, W. and Berg, D.J. and Rennick, D.M.
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.
Keywords:CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Colitis, Colon, Cytokines, DNA-Binding Proteins, Helper-Inducer T-Lymphocytes, Inflammatory Bowel Diseases, Interleukin-10, Passive Immunization, Proteins, T-Lymphocyte Subsets, alpha-beta T-Cell Antigen Receptors, Animals, Mice
Source:Journal of Experimental Medicine
Publisher:Rockefeller University Press
Page Range:241-251
Date:1 July 1996
Official Publication:https://doi.org/10.1084/jem.184.1.241
PubMed:View item in PubMed

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