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Intestinal T Cells Differentiate and Rearrange Antigen Receptor Genes In Situ in the Human Infant¹

Amanda M. Williams^2,*, Paul W. Bland^,, Anne C. Phillips, Susan Turner^*, Trevor Brooklyn^*, Gabriel Shaya^*, Richard D. Spicer and Christopher S. J. Probert^*

Departments of ^* Clinical Science at South Bristol and Clinical Veterinary Science, University of Bristol, and Department of Paediatric Surgery, Bristol Royal Hospital for Children, Bristol, United Kingdom; and Department of Clinical Immunology, University of Gothenburg, Gothenburg, Sweden

Intestinal Ag exposure during neonatal life influences appropriate adult immune responses. To define the mechanisms shaping the T cell repertoire during this period, we examined T cell differentiation and receptor diversity in the intestine of human infants. Developmental phenotypes of intraepithelial and lamina propria intestinal T cells from infants aged 1 day to 2 years were assessed ex vivo by flow cytometry and in situ by triple-fluorescent immunohistochemistry. Gene recombination-specific enzymes were assessed by PCR. TCR -chain V region gene diversity was determined by sequencing. Several different early lineage T cell populations were present neonatally: CD3⁺4^–8^– T cells were present at birth and numbers decreased during the neonatal period; CD3⁺4⁺8⁺ T cells were present in low numbers throughout infancy; and CD3⁺4⁺8^– or CD3⁺4^–8⁺ T cells increased with age. Very early lineage T cells, CD3^–2^–7⁺ and CD3^–2⁺7⁺, were present neonatally, but were essentially absent at 1 year. Most lamina propria T cells differentiated rapidly after birth, but maturation of intraepithelial T cells took place over 1 year. Intestinal samples from infants less than 6 mo old contained transcripts of T early and TdT, and 15 of 19 infant samples contained mRNA for RAG-1, some coexpressing RAG-2. TCR -chain repertoires were polyclonal in infants. Immature T cells, pre-T cells, and genes involved in T cell recombination were found in the intestine during infancy. T cell differentiation occurs within the neonatal human intestine, and the TCR repertoire of these developing immature T cells is likely to be influenced by luminal Ags. Thus, mucosal T cell responsiveness to environmental Ag is shaped in situ during early life.

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The JI 2004 173: 7107-7108. [Full Text]  

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