Cell
Volume 75, Issue 2, 22 October 1993, Pages 263-274
Journal home page for Cell

Article
Interleukin-10-deficient mice develop chronic enterocolitis

https://doi.org/10.1016/0092-8674(93)80068-PGet rights and content

Summary

Interleukin-10 (IL-10) affects the growth and differentiation of many hemopoietic cells in vitro; in particular, it is a potent suppressor of macrophage and T cell functions. In IL-10-deficient mice, generated by gene targeting, lymphocyte development and antibody responses are normal, but most animals are growth retarded and anemic and suffer from chronic enterocolitis. Alterations in intestine include extensive mucosal hyperplasia, inflammatory reactions, and aberrant expression of major histocompatibility complex class II molecules on epithelia. In contrast, mutants kept under specific pathogen-free conditions develop only a local inflammation limited to the proximal colon. These results indicate that the bowel inflammation in the mutants originates from uncontrolled immune responses stimulated by enteric antigens and that IL-10 is an essential immunoregulator in the intestinal tract.

References (54)

  • DialynasD.P. et al.

    Characterization of the murine T cell surface molecule, designated L3T4, identified by monoclonal antibody GK1.5: similarity of L3T4 to the human Leu-3/T4 molecule

    J. Immunol.

    (1983)
  • FinkelmanF.D. et al.

    Suppression of in vivo polyclonal IgE responses by monoclonal antibody to the lymphokine B-cell stimulatory factor 1

  • FiorentinoD.F. et al.

    Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones

    J. Exp. Med.

    (1989)
  • FiorentinoD.F. et al.

    IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells

    J. Immunol.

    (1991)
  • FiorentinoD.F. et al.

    IL-10 inhibits cytokine production by activated macrophages

    J. Immunol.

    (1991)
  • FörsterI. et al.

    Flow cytometric analysis of cell proliferation dynamics in the B cell compartment of the mouse

    Int. Immunol.

    (1989)
  • GazzinelliR.T. et al.

    IL-10 inhibits parasite killing and nitric oxide production by IFN-γ-activated macrophages

    J. Immunol.

    (1992)
  • GillisS. et al.

    Long term culture of tumour-specific cytotoxic T cells

    Nature

    (1977)
  • GoN.F. et al.

    Interleukin 10 (IL-10), a novel B cell stimulatory factor: unresponsiveness of X chromosome-linked immunodeficiency B cells

    J. Exp. Med.

    (1990)
  • GrützmannR.

    Vergleichende idiotypische Analyse von Rezeptoren mit Spezifität für Histokompatibilitätsantigene

  • HeinzelF.P. et al.

    Production of interferon-γ, interleukin 2, interleukin 4, and interleukin 10 by CD4+ lymphocytes in vivo during healing and progressive murine leishmaniasis

  • HowardM. et al.

    Interleukin-10 protects mice from lethal endotoxemia

    J. Exp. Med.

    (1993)
  • HsiehC.S. et al.

    Differential regulation of T helper phenotype development by interleukins 4 and 10 in an αβ T-cell-receptor transgenic system

  • HsiehC.S. et al.

    Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages

    Science

    (1993)
  • HsuS.M. et al.

    Use of avidin—biotin—peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedure

    Histochem. Cytochem.

    (1981)
  • HuangS. et al.

    Immune response in mice that lack the interferon-γ receptor

    Science

    (1993)
  • IshidaH. et al.

    Continuous anti-interleukin-10 antibody administration depletes mice of Ly-1 B cells but not conventional B cells

    J. Exp. Med.

    (1992)
  • Cited by (0)

    View full text