Development of CD8 α α+ intestinal intraepithelial T cells in β 2-microglobulin- and/or TAP1-deficient mice

Abstract

The development of CD8+ intestinal intraepithelial T lymphocytes (IEL) was analyzed in mice that are deficient in the expression of MHC class I molecules, owing to either a mutated β 2-microglobulin (β 2m) gene or a mutated transporter associated with Ag processing 1 (TAP1) gene, and in mice doubly homozygous for β 2m and TAPI mutations. In all mutant mice, the population size of major CD8 α α+ and CD8 αβ+ αβ-IEL subsets was reduced drastically, and this resulted in a conspicuous decrease in the total number of αβ-IEL. Concomitantly, a compensatory two- to threefold increase in the number of γ δ-IEL consisting mostly of CD8 α α+ subset was noted. In radiation bone marrow chimeras, this wild-type/mutant phenotype was determined by the genotype of radioresistant host cells, but was not determined by the genotype of reconstituting bone marrow-derived cells. In β 2m X TCR-δ double mutant mice, however, the CD8 α α+ but not CD8 αβ+ αβ-IEL subset expanded dramatically. Thus, in the absence of γ δ-IEL, αβ-IEL in β 2m-deficient mice outnumbered those in wild-type littermates. These results indicate that the generation of CD8 α α+ lymphocyte population of αβ- and γ δ-IEL is not dependent, but that of CD8 αβ+ lymphocyte population of αβ-IEL is dependent on β 2m- and/or TAP1-dependent MHC class I molecules, expressed by the controlling cells present in the anatomical site, where the development of IEL takes place.