Extrathymic T cell differentiation in the human intestine early in life

Duncan Howie, Jo Spencer, Denise DeLord, Costantino Pitzalis, Neville C. Wathen, Ahmet Dogan, Arne Akbar, Thomas T. MacDonald

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Abstract

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-α. 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-β 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-α 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.

Original languageEnglish (US)
Pages (from-to)5862-5872
Number of pages11
JournalJournal of Immunology
Volume161
Issue number11
StatePublished - Dec 1 1998

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Howie, D., Spencer, J., DeLord, D., Pitzalis, C., Wathen, N. C., Dogan, A., Akbar, A., & MacDonald, T. T. (1998). Extrathymic T cell differentiation in the human intestine early in life. Journal of Immunology, 161(11), 5862-5872.