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Signals from the IL-9 Receptor Are Critical for the Early Stages of Human Intrathymic T Cell Development¹

Magda De Smedt^*, Bruno Verhasselt^*, Tessa Kerre^*, Dominique Vanhecke^*, Evelien Naessens^*, Georges Leclercq^*, Jean-Christophe Renauld, Jacques Van Snick and Jean Plum^2,*

^* Department of Clinical Chemistry, Microbiology and Immunology, University of Ghent, University Hospital of Ghent, Ghent, Belgium; and Ludwig Institute for Cancer Research, Brussels Branch and Experimental Medicine Unit, Catholic University of Louvain, Brussels, Belgium

Highly purified human CD34⁺ hemopoietic precursor cells differentiate into mature T cells when seeded in vitro in isolated fetal thymic lobes of SCID mice followed by fetal thymus organ culture (FTOC). Here, this chimeric human-mouse FTOC was used to address the role of IL-9 and of the -chain of the IL-9 receptor (IL-9R) in early human T cell development. We report that addition of the mAb AH9R7, which recognizes and blocks selectively the human high affinity -chain of the IL-9R, results in a profound reduction of the number of human thymocytes. Analysis of lymphoid subpopulations indicates that a highly reduced number of cells undergo maturation from CD34⁺ precursor cells toward CD4⁺CD3^-CD8^-CD1⁺ progenitor cells and subsequently toward CD4⁺CD8⁺ double positive (DP) thymocytes. Addition of IL-9 to the FTOC resulted in an increase in cell number, without disturbing the frequencies of the different subsets. These data suggest that IL-9R signaling is critical in early T lymphoid development.

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