A PANCOLITIS RESEMBLING HUMAN ULCERATIVE-COLITIS (UC) IS INDUCED BY CD4(-BETA T-CELLS OF ATHYMIC ORIGIN IN HISTOCOMPATIBLE SEVERE COMBINED IMMUNODEFICIENT (SCID) MICE() TCR ALPHA)

CD4(+) TCR alpha beta(+) T cells from the colonic lamina propria of at hymic (nude) mice were adoptively transferred into histocompatible (SC ID) mice homozygous for the autosomal recessive mutation scid (severe combined immunodeficiency). Transfer of these extrathymic CD4(+) T cel ls into SCID mice induced a pancolitis in the adoptive host. The histo pathology of this inflammatory response was restricted to the colon an d closely resembled human UC. CD4(+) T cells infiltrating the colonic lamina propria of diseased SCID mice displayed the surface phenotype o f mucosa-seeking memory/effector cells, expressed interferon-gamma (IF N-gamma), and lysed targets in a Fas (CD95)/FasL-dependent pathway. Ma ssive accumulation of oligoclonal CD4(+) T cells of athymic origin wit h the phenotype of Th1 memory/effector T cells in the colonic lamina p ropria of a histocompatible, immunodeficient host elicits a pancolitis that morphologically mimics human UC.