Understanding immune-microbial homeostasis in intestine.
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 Th 1 cells. Manyquestions 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?
Elson
Charles O
CO
Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, 35294-0007, USA. coelson@uab.edu
Cong
Yingzi
Y
D000818:Animals; D000942:Antigens, Bacterial; D003092:Colitis / Q000276:immunology / Q000382:microbiology; D006706:Homeostasis; D018928:Immunity, Mucosal; D007422:Intestines / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D008809:Mice, Inbred C3H; D018448:Models, Immunological; D013601:T-Lymphocytes / Q000276:immunology
D000942:Antigens, Bacterial