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J. Exp. Med.,
Volume 188, Number 2, July 20, 1998 255-265
By


§
From the * Department of Microbiology and Immunology and the The differentiation of intestinal intraepithelial lymphocytes (IEL) remains controversial, which
may be due in part to the phenotypic complexity of these T cells. We have investigated here the development of IEL in mice on the recombination activating gene (RAG)-2
Division of Digestive Diseases,
Department of Medicine, University of California at Los Angeles, Los Angeles, California 90095;
and the § La Jolla Institute for Allergy and Immunology, San Diego, California 92121
/
background which express a T cell antigen receptor (TCR) transgene specific for an H-Y peptide
presented by Db (H-Y/Db × RAG-2
mice). In contrast to the thymus, the small intestine in
female H-Y/Db × RAG-2
mice is severely deficient in the number of IEL; TCR transgene+
CD8
and CD8
are virtually absent. This is similar to the number and phenotype of IEL
in transgenic mice that do not express the Db class I molecule, and which therefore fail positive
selection. Paradoxically, in male mice, the small intestine contains large numbers of TCR+ IEL
that express high levels of CD8
homodimers. The IEL isolated from male mice are functional, as they respond upon TCR cross-linking, although they are not autoreactive to stimulator cells from male mice. We hypothesize that the H-Y/Db TCR fails to undergo selection in
IEL of female mice due to the reduced avidity of the TCR for major histocompatibility complex peptide in conjunction with the CD8
homodimers expressed by many cells in this lineage. By contrast, this reduced TCR/CD8
avidity may permit positive rather than negative
selection of this TCR in male mice. Therefore, the data presented provide conclusive evidence
that a TCR which is positively selected in the thymus will not necessarily be selected in IEL,
and furthermore, that the expression of a distinct CD8 isoform by IEL may be a critical determinant of the differential pattern of selection of these T cells.
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