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Mucosal Immunol ; 4(1): 93-101, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20737000

ABSTRACT

Intestinal CD8αα intraepithelial T lymphocytes (T-IELs) have a key role in mucosal immunity and, unlike other T cells, were proposed to differentiate locally. In apparent contradiction, these cells were also shown to originate from a wave of thymus migrants colonizing the gut in the first 3 weeks after birth. We here identify previously uncharacterized very immature CD4(-)CD8(-)CD3(-)CD44(+)CD25(int) thymocytes, which have not yet rearranged their T-cell antigen receptor (TCR), as having the capacity to leave the thymus, migrate to the blood, colonize the gut, and reconstitute CD8αα T-IEL, and show that this cell set is fully responsible for the generation of the CD8αα T-IEL pool. Thus, although the thymus may be fundamental for efficient T-cell commitment, CD8αα T-IEL' complete TCR rearrangements and TCR-αß/γδ lineage commitment must occur in the gut. These results demonstrate a major role of the gut environment as a primary lymphoid organ.


Subject(s)
CD8 Antigens/immunology , CD8-Positive T-Lymphocytes/immunology , Hyaluronan Receptors/immunology , Intestinal Mucosa/immunology , Intestines/immunology , Lymphoid Tissue/immunology , Animals , Antigens, Differentiation, T-Lymphocyte/genetics , Base Sequence , Cell Differentiation , Mice , Mice, Knockout , Polymerase Chain Reaction , Receptors, Antigen, T-Cell/immunology , T-Lymphocytes/immunology , Thymus Gland/immunology
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