Understanding immune-microbial homeostasis in intestine
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The mechanisms concerning how the immune system is able to deal with the massive antigen challenge represented by the commensal bacterial flora have been a mystery. Recently a number of animal models with impairment of these mechanisms have been identified. One of these is the C3H/HeJBir mouse, which, under certain environmental conditions, can spontaneously develop colitis, which later remits. These mice show increased B cell and T cell reactivity to antigens of the enteric bacterial flora. CD4+ T cells from this strain cause colitis, when activated by enteric bacterial antigens and transferred to histocompatible severe combined immunodeficiency recipients. This colitis is mediated by CD4+ Th1 cells and requires a sustained mucosal production of interleukin-12, which, in turn, is dependent on CD40L-CD40 interactions in the gut. Regulatory T cells that appear to limit the colitis have been identified and have the properties of the T-regulatory-1 subset. Functional Tr1 activity for bacterial antigens is present in the lamina propria CD4+ T cells. These Tr1 cells may exert their effects by inhibition of dendritic cell function in the mucosa, rather than by direct effects on Th1 cells. Many questions remain to be answered, including, How do the enteric bacterial-host interactions shape the immune system for abnormal responses such as inflammatory bowel disease, autoimmunity, and allergy?
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- Understanding immune-microbial homeostasis in intestine
Volume 26, Issue 1-3 , pp 87-94
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