A pancolitis resembling human ulcerative colitis (UC) is induced by CD4+ TCR alphabeta T cells of athymic origin in histocompatible severe combined immunodeficient (SCID) mice.
massive accumulation of oligoclonal CD4+ T cells of athymic origin with the phenotype of Th1 memory/effector T cells in the colonic lamina propria of a histocompatible, immunodeficient host elicits a pancolitis that morphologically mimics human UC.
Abstract
CD4+ TCRalphabeta+ T cells from the colonic lamina propria of athymic (nude) mice were adoptively transferred into histocompatible (SCID) mice homozygous for the autosomal recessive mutation scid (severe combined immunodeficiency). Transfer of these extrathymic CD4+ T cells into SCID mice induced a pancolitis in the adoptive host. The histopathology of this inflammatory response was restricted to the colon and closely resembled human UC. CD4+ T cells infiltrating the colonic lamina propria of diseased SCID mice displayed the surface phenotype of mucosa-seeking memory/effector cells, expressed interferon-gamma (IFN-gamma), and lysed targets in a Fas (CD95)/FasL-dependent pathway. Massive accumulation of oligoclonal CD4+ T cells of athymic origin with the phenotype of Th1 memory/effector T cells in the colonic lamina propria of a histocompatible, immunodeficient host elicits a pancolitis that morphologically mimics human UC.