Signals from the IL-9 receptor are critical for the early stages of human intrathymic T cell development

Highly purified human CD34(+) hemopoietic precursor cells differentiate int o mature T cells when seeded in vitro in isolated fetal thymic lobes of SCI D mice followed by fetal thymus organ culture (FTOC). Here, this chimeric h uman-mouse FTOC was used to address the role of IL-9 and of the alpha-chain of the IL-9 receptor (IL-9R alpha) in early human T cell development. We r eport that addition of the mAb AH9R7, which recognizes and blocks selective ly the human high affinity alpha-chain of the IL-9R, results in a profound reduction of the number of human thymocytes, Analysis of lymphoid subpopula tions indicates that a highly reduced number of cells undergo maturation fr om CD34(+) precursor cells toward CD4(+)CD3(-)CD8(-)CD1(+) progenitor cells and subsequently toward CD4(+)CD8(+) double positive (DP) thymocytes. Addi tion of IL-9 to the FTOC resulted in an increase in cell number, without di sturbing the frequencies of the different subsets. These data suggest that IL-9R alpha signaling is critical in early T lymphoid development.