DEVELOPMENT OF CD8-ALPHA-ALPHA(-CELLS IN BETA(2)-MICROGLOBULIN-DEFICIENT AND() INTESTINAL INTRAEPITHELIAL T)OR TAP1-DEFICIENT MICE/

The development of CD8(+) intestinal intraepithelial T lymphocytes (IE L) was analyzed in mice that are deficient in the expression of MHC cl ass I molecules, owing to either a mutated beta(2)-microglobulin (beta (2)m) gene or a mutated transporter associated with Ag processing 1 (T AP1) gene, and in mice doubly homozygous for beta(2)m and TAP1 mutatio ns. In all mutant mice, the population size of major CD8 alpha alpha() and CD8 alpha beta(+) alpha beta-IEL subsets was reduced drastically , and this resulted in a conspicuous decrease in the total number of a lpha beta-IEL. Concomitantly, a compensatory two- to threefold increas e in the number of gamma delta-IEL consisting mostly of CD8 alpha alph a(+) subset was noted. In radiation bone marrow chimeras, this wild-ty pe/mutant phenotype was determined by the genotype of radioresistant h ost cells, but was not determined by the genotype of reconstituting bo ne marrow-derived cells. In beta(2)m x TCR-delta double mutant mice, h owever, the CD8 alpha alpha(+) but not CD8 alpha beta(+) alpha beta-IE L subset expanded dramatically. Thus, in the absence of gamma delta-IE L, alpha beta-IEL in beta(2)m-deficient mice outnumbered those in wild -type littermates. These results indicate that the generation of CD8 a lpha alpha(+) lymphocyte population of alpha beta- and gamma delta-IEL is not dependent, but that of CD8 alpha beta(+) lymphocyte population of alpha beta-IEL is dependent on beta(2)m- 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.