[PDF][PDF] T cells in inflammatory bowel disease: protective and pathogenic roles

F Powrie - Immunity, 1995 - core.ac.uk
F Powrie
Immunity, 1995core.ac.uk
The immune system is exposed to an enormous number of antigens in the intestine,
including those derived from food and bacteria, yet mucosal immune responses are
characterized by a lack of cell-mediated immune responsiveness to these antigens. Indeed,
oral exposure to antigen can lead to a subsequent state of systemic hyporeactivity to the fed
antigen (Weiner, 1994) suggesting that there are regulatory mechanisms in place that
actively prevent development of immune responses to antigens present in the gut. In the last …
The immune system is exposed to an enormous number of antigens in the intestine, including those derived from food and bacteria, yet mucosal immune responses are characterized by a lack of cell-mediated immune responsiveness to these antigens. Indeed, oral exposure to antigen can lead to a subsequent state of systemic hyporeactivity to the fed antigen (Weiner, 1994) suggesting that there are regulatory mechanisms in place that actively prevent development of immune responses to antigens present in the gut.
In the last 2 years, an impressive number of different models of inflammatory bowel disease (IBD) in mice and rats have been described. These can broadly be divided into three groups. First, mice with alterations in T cell subpopulations and T cell selection: T cell receptor-a (TCRa) chain-deficient mice, TCR6 chain-deficient mice, and major histocompatibility complex (MHC) class II genedeficient mice (Mombaerts et al., 1993) SCID mice restored with CD45RBh’CD4’T cells (Morrissey et al., 1993; Powrie et al., 1993, 1994a), HLA-B27 transgenic rats (Hammer et al., 1990) and human CD3s transgenic mice, transplanted with normal Fl bone marrow cells (Hollander et al., 1995a). Second, mice with targeted disruption of cytokine genes: interleukin-2 (IL-2)(Sadlack et al., 1993) IL-10 (Kuhn et al., 1993) and transforming growth factor-51 (TGF61)-deficient mice (Shull et al., 1992; Kulkarni et al., 1993). Third, mice lacking signaling proteins; G protein subunit Ga3-deficient mice (Rudolph et al., 1995). While these models at first sight look very different, they all involve manipulations that perturb the immune system. Indeed, all of these models of IBD may induce disease by the common feature of disrupting a Tcell-dependent regulatory system that normally functions to protect the gut from cell-mediated immune attack.
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