Development and physiological role of gammadeltaT cells.

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Our result shows :1) The absence of gammadelta-IEL is associated with a reduction in intestinal epithelial cell turnover and a downregulation of the expression of MHC class II molecules.2) The development of CD8^+ intestinal intraepitehlial T lymphocytes (IEL) was analyzed in mice that are deficient in the expression of MHC class I molecules owing to either a mutanted beta_2M gene or a mutanted TAP-1 gene and in mice doubly lomozygous for beta_2M and TAP-1 mutations. In all mutant mice, the population size of major CD8alphaalpha^+ and CD8alphabeta^+ alphabeta-IEL subsets was drastically reduced. In beta_2M*TCRdelta double mutant mice, however, the CD8alphaalpha^+ but not CD8alphabeta^+alphabeta-IEL subset expanded dramatically. Thus, in the absence of gammadelta-IEL,alphabeta-IEL in beta_2M deficient mice outnumbered those in wild-type littermates. These results indicate that the generation of CD8alphaalpha^+ lymphocyte population of alphabeta- and gammadelta-IEL is not dependent but t … More hat of CD8alphabeta^+ lymphocyte population of alphabeta-IEL is dependent on beta_2M- and/or TAP-1 dependent MHC class I molecules expressed by the controlling cells present in the anatomical site where the development of IEL takes place.3) After intradermal injection of the autoreactive T cells, delta^<-/-> mice developed significantly enhanced DTH responses and cutaneous GVHD,which persisted longer than those in delta^<+/-> mice. Surprisingly, resistance to the cutaneous GVHD was not induced in the epidermis of delta^<-/-> mice after spontaneous recovery from the GVHD,while the "susceptible" epidermis of delta^<-/-> mice contained large numbers of alphabeta^+ dEC comparable to those in the "resistant" epidermis of delta^<+/-> mice. Injection of day 16 fetal thymocytes from delta^<+/+> mice into delta^<-/-> mice resulted in the appearance of donor-type gammadelta^+ dEC in the epidermis and the reconstitution with the gammadelta^+ dEC restored the protective immune response of the epidermus against the GVHD to nearly normal levels. These results indicate that gammadelta^+ dEC are responsible for the site-restricted protection against cutaneous GVHD. Less