Antigen-specific human T-cell responses and T cell-dependent production of human antibodies in a humanized mouse model.
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 (DNP(23)-KLH). Human T cells from DNP(23)-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.
Tonomura
Noriko
N
Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, MGH-East, Boston, MA 02129, USA.
Habiro
Katsuyoshi
K
Shimizu
Akira
A
Sykes
Megan
M
Yang
Yong-Guang
YG
D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D000941:Antigens / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D006413:Hematopoietic System / Q000166:cytology / Q000276:immunology; D006801:Humans; D007114:Immunization; D008099:Liver / Q000166:cytology; D016031:Liver Transplantation; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D016513:Mice, SCID; D023421:Models, Animal; D013601:T-Lymphocytes / Q000276:immunology*
D000941:Antigens; D000939:Epitopes