Extrathymic T cell differentiation in the human intestine early in life.
It is clear from experimental studies in mice that T cell maturation can occur outside the thymus, especially in the intestine. There is little sound evidence so far that extrathymic T cell maturation occurs to any significant extent in human gut, and, postnatally, there is abundant evidence that the gut mucosa is an immune effector organ. Here, we describe a large population of T lymphocytes in human fetal intestinal mucosa that are proliferating (Ki67+) in the absence of foreign Ag (CD3+, Ki67+ lamina propria lymphocytes (LPL) 22 +/- 1.8% and CD3+, Ki67+ intraepithelial lymphocytes (IEL) 9.1 +/- 1.4%), that express the T cell activation markers CD103, HLA-DR, and L-selectin(low), and that express mRNA transcripts for pre-TCR-alpha. There is also a substantial proportion of CD7+ LPLs that do not express CD3 (CD3-7+, 14 +/- 7% of all LPLs) in the fetal gut that may be differentiating into CD3+ cells. Rearranged TCR-beta transcripts of fetal LPLs, IELs, and paired blood lymphocytes were cloned and sequenced, and virtually no overlap of clonality was observed between blood and intestine, suggesting that gut T cells may not be derived from the blood. In addition, 30 days after engraftment of SCID mice with fetal intestine, CD3-7+ cells, proliferating T cells, and pre-TCR-alpha transcripts were abundant, and there is a threefold increase in CD3+ IELs. These data show that in the human intestine before birth a population of precursor T cells exists that may be differentiating into mature T cells in situ.
Howie
D
D
Department of Paediatric Gastroenterology, St. Bartholomew's and the Royal London School of Medicine and Dentistry, United Kingdom.
Spencer
J
J
DeLord
D
D
Pitzalis
C
C
Wathen
N C
NC
Dogan
A
A
Akbar
A
A
MacDonald
T T
TT
D000375:Aging / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005314:Embryonic and Fetal Development / Q000235:genetics / Q000276:immunology; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000276:immunology; D019674:Genes, T-Cell Receptor beta / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology; D007583:Jejunum / Q000166:cytology* / Q000276:immunology* / Q000637:transplantation; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008969:Molecular Sequence Data; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000637:transplantation; D013950:Thymus Gland / Q000166:cytology; D014158:Transcription, Genetic / Q000276:immunology