Induction of TCR-gamma delta expression on triple-negative (CD3-4-8-) human thymocytes. Comparative analysis of the effects of IL-4 and IL-7.

It is well established that IL-4 and IL-7 control the differentiation of TCR-gamma delta-expressing cells from CD3/TCR-negative thymic precursors. In this study, we have compared the in situ expression of IL-4 and IL-7 mRNA in human postnatal thymus with the in vitro effect of IL-4 and IL-7 on the expansion of TCR-gamma delta + cells from highly purified CD3-4-8- triple-negative thymocytes. IL-4 mRNA expression was restricted to subcapsular regions of the human thymus, whereas cells expressing IL-7 mRNA were distributed throughout the thymic tissue, with some enrichment in subcapsular and cortical regions. Epithelial cells of the outer layer of Hassall's corpuscle strongly expressed IL-7 mRNA. IL-7 but not IL-4 or IL-2, stimulated strong proliferative activity and cellular expansion of triple-negative thymocytes. All three induced the appearance of TCR-gamma delta + cells within 4 days of culture. In the presence of IL-4 or IL-2, 30 to 55% of viable cells were TCR-gamma delta + after 5 to 9 days, whereas only 10 to 15% triple-negative thymocytes cultured with IL-7 expressed TCR-gamma delta. However, comparable absolute numbers of viable TCR-gamma delta + thymocytes were recovered when triple-negative thymocytes were cultured with IL-4 or IL-7, but not with IL-2. Taken together, our results suggest that IL-4 and IL-7 (both of which are produced in situ in thymic tissue) play equally important roles in the in vitro generation of TCR-gamma delta + thymocytes from triple-negative precursor cells.