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International Immunology, Vol. 14, No. 10, pp. 1113-1124, October 2002
© 2002 Japanese Society for Immunology

The in vivo development of human T cells from CD34+ cells in the murine thymic environment

Yuki Saito1,3, Yoshie Kametani1,2, Katsuto Hozumi1, Naoko Mochida1,2, Kiyoshi Ando2,4, Mamoru Ito5, Tatsuji Nomura5, Yutaka Tokuda2,3, Hiroyasu Makuuchi3, Tomoo Tajima3 and Sonoko Habu1

1 Department of Immunology, 2 Research Center for Genetic Engineering and Cell Transplantation, 3 Department of Surgery, and 4 Department of Hematology and Rheumatology, Tokai University School of Medicine, Kanagawa 259-1193, Japan 5 Central Institute for Experimental Animals, Kanagawa 259-1193, Japan

Correspondence to: S. Habu, Bohseidai, Isehara, Kanagawa 259-1193, Japan. E-mail: sonoko{at}is.icc.u-tokai.ac.jp
Transmitting editor: K. Okumura

There is increasing evidence that human hematopoietic stem cells can develop into lymphocytes expressing T cell surface markers in the organ culture of murine embryonic thymic lobes. If human T cells with functional maturity are inducible from human stem cells in the mouse, it may be a useful model to investigate human T cell development and the human immune response in vivo. To approach this, we produced a hybrid cluster of murine fetal thymic epithelial cells and human cord blood-derived CD34+ cells (hu/m cluster) using reaggregate thymic organ culture, and subsequently implanted it under the kidney capsule of NOD/SCID mice. The implanted hu/m cluster grew in volume under the kidney capsule and contained increased numbers of CD4+CD8+cells as well as CD4 or CD8 single-positive cells with low CD1a expression. These lymphocytes were also shown to possess activity for producing IL-2 and IL-4. Characteristics similar to human T cells also developed in the thymus of newly established mice lacking NK activity from NOD/SCID mice. These results indicate that functionally mature T cells can develop in vivo from human hematopoietic progenitors in the murine environment composed of thymic epithelial cells.

Keywords: human, T lymphocyte, thymus, transplantation


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