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*
Departments of Paediatric Gastroenterology and
Obstetrics and Gynaecology, St. Bartholomew’s and the Royal London School of Medicine and Dentistry, London, United Kingdom; Departments of
Histopathology, and
§
Rheumatology, Guy’s, King’s College and St. Thomas’ Hospital, Medical and Dental School, London, United Kingdom;
¶
Department of Histopathology, University College London, London, United Kingdom; and
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Department of Clinical Immunology, Royal Free School of Medicine, London, United Kingdom
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-selectinlow, and that express mRNA
transcripts for pre-TCR-
. 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-ß 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- 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
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