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Bacteria-triggered CD4(+) T regulatory cells suppress Helicobacter hepaticus-induced colitis

  1. Author:
    Kullberg, M. C.
    Jankovic, D.
    Gorelick, P. L.
    Caspar, P.
    Letterio, J. J.
    Cheever, A. W.
    Sher, A.

  2. Author Address

    NIAID, Immunobiol Sect, Lab Parasit Dis, NIH, Bldg 50,Rm 6146,50 S Dr, Bethesda, MD 20892 USA NIAID, Immunobiol Sect, Lab Parasit Dis, NIH, Bethesda, MD 20892 USA NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA Sci Applicat Int Corp, NCI Frederick, Lab Anim Sci Program, Anim Hlth Diagnost Lab, Ft Detrick, MD 21702 USA Biomed Res Inst, Rockville, MD 20852 USA Kullberg MC NIAID, Immunobiol Sect, Lab Parasit Dis, NIH, Bldg 50,Rm 6146,50 S Dr, Bethesda, MD 20892 USA
    1. Year: 2002
  2. Journal: Journal of Experimental Medicine
    1. 196
    2. 4
    3. Pages: 505-515
  4. Type of Article: Article
  1. Abstract:

    We have previously demonstrated that interleukin (IL)-10- deficient (IL-10 knockout [KO]) but not wild-type (WT) mice develop colitis after infection with Helicobactor hepaticus. Here, we show that infected recombination activating gene (RAG) KO mice develop intestinal inflammation after reconstitution with CD4(+) T cells from IL-10 KO animals and that the cotransfer of CD4(+) T cells from H. hepaticus-infected but not uninfected WT mice prevents this colitis. The disease- protective WT CD4(+) cells are contained within the CD45RB(low) fraction and unexpectedly were found in both the CD25(+) and the CD25(-) subpopulations of these cells, their frequency being higher in the latter. The mechanism by which CD25(+) and CD25(-) CD45RB(low) CD4(+) cells block colitis involves IL-10 and not transforming growth factor (TGF)-beta, as treatment with anti-IL-IOR, but not anti-TGF-beta monoclonal antibody abrogated their protective effect. In vitro, CD45RB(low) CD4(+) cells from infected WT mice were shown to produce IL-10 and suppress interferon-gamma production by IL-10 KO CD4(+) cells in an H. hepaticus antigen-specific manner. Together, our data support the concept that H. hepaticus infection results in the induction in WT mice of regulatory T cells that prevent bacteria-induced colitis. The induction of such cells in response to gut flora may be a mechanism protecting normal individuals against inflammatory bowel disease.

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