The role of the gut as a primary lymphoid organ: CD8αα intraepithelial T lymphocytes in euthymic mice derive from very immature CD44+ thymocyte precursors.
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-αβ/γδ lineage commitment must occur in the gut. These results demonstrate a major role of the gut environment as a primary lymphoid organ.
Peaudecerf
L
L
INSERM, U1020, Medical Faculty Descartes Paris V, Paris, France.
dos Santos
P Ribeiro
PR
Boudil
A
A
Ezine
S
S
Pardigon
N
N
Rocha
B
B
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics; D001483:Base Sequence; D016827:CD8 Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D018960:Hyaluronan Receptors / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology*; D007422:Intestines / Q000276:immunology*; D008221:Lymphoid Tissue / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology
D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; D018960:Hyaluronan Receptors; D011948:Receptors, Antigen, T-Cell