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 Blood, 15 April 2008, Vol. 111, No. 8, pp. 4293-4296.
Prepublished online as a Blood First Edition Paper on February 12, 2008; DOI 10.1182/blood-2007-11-121319.

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IMMUNOBIOLOGY

Brief Report

Antigen-specific human T-cell responses and T cell–dependent production of human antibodies in a humanized mouse model

Noriko Tonomura1,*, Katsuyoshi Habiro1,*, Akira Shimizu1, Megan Sykes1, and Yong-Guang Yang1

1 Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston

Humanized mice with a functional human immune system would be very useful for in vivo studies of human immunobiology. We have previously shown that cotransplantation of human fetal thymus/liver tissues and CD34+ fetal liver cells into immunodeficient nonobese diabetic severe combined immunodeficiency (NOD/SCID) mice leads to the development of multiple lineages of human lymphohematopoietic cells and formation of secondary lymphoid organs with normal architecture. Here, we evaluated the ability of these humanized mice to develop antigen-specific, T cell–dependent antibody responses after in vivo immunization with T-dependent antigen, 2,4-dinitrophenyl hapten-keyhole limpet hemocyanin (DNP23-KLH). Human T cells from DNP23-KLH–immunized mice showed strong proliferation in response to KLH in vitro. Furthermore, T cell–dependent production of DNP-specific human antibodies (mainly IgG1 and IgG2) was detected in all immunized mice. These results confirm that a functional human immune system can be established in immunodeficient mice through cotransplantation of human fetal thymus/liver tissues and CD34+ hematopoietic stem/progenitor cells.


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