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

Abstract

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 lymphohema-topoietic 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 lgG1 and lgG2) 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. © 2008 by The American Society of Hematology.