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Phenotypic Characterization of CD3^–7⁺ Cells in Developing Human Intestine and an Analysis of Their Ability to Differentiate into T Cells ¹

Ute Gunther^*, Judith A. Holloway^*, John G. Gordon^*, Andrea Knight^*, Victoria Chance^*, Neil A. Hanley, David I. Wilson, Ruth French, Jo Spencer^¶, Howard Steer, Graham Anderson^|| and Thomas T. MacDonald^2,*

Divisions of ^* Infection, Inflammation and Repair, Human Genetics, and Cancer Sciences, Department of Surgery, University of Southampton, Southampton; ^¶ Department of Immunobiology, GKT School of Medicine, London, United Kingdom; and ^|| Department of Anatomy, University of Birmingham, Birmingham, United Kingdom

We have identified a large population of CD3^–7⁺ cells in human fetal gut. Three- and four-color flow cytometry revealed a distinct surface Ag profile on this population; the majority were negative for CD4 and CD8, whereas most of the remainder expressed the CD8 homodimer. In contrast about half of CD3⁺ cells expressed CD4 and half expressed CD8. A large proportion of CD3^–7⁺ cells expressed CD56, CD94, and CD161, and whereas CD3⁺ T cells also expressed CD161, they only rarely expressed CD56 or CD94. Further studies were conducted to determine whether the CD3^–7⁺ cells have the potential to differentiate into CD3⁺ cells. About half of CD3^–7⁺ cells contain intracellular CD3. Rearranged TCR -chains were detected in highly purified CD3^–7⁺ cells as an early molecular sign of T cell commitment, and the pattern of rearrangement with V regions spliced to the most 5' J segment is reminiscent of early thymocyte differentiation. In reaggregate thymic organ cultures, CD3^–7⁺ cells also gave rise to CD3⁺ T cells. Thus, we demonstrate that the CD3^–7⁺ cells present in the human fetal gut display a distinct phenotype and are able to develop into CD3⁺ T cells.

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