Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.
Antigen-specific B and T cells in human/mouse radiation chimera following immunization in vivo.
Immunology. 1999 Apr;96(4):634-41. Unique Identifier : AIDSLINE MED/99250349 Bocher WO; Marcus H; Shakarchy R; Dekel B; Shouval D; Galun E; Reisner Y; Department of Immunology, The Weizmann Institute of Science,; Rehovot, Israel.
Abstract:
Adoptive transfer of human peripheral blood mononuclear cells (PBMC) into mice with severe combined immunodeficiency (SCID) or into lethally irradiated BALB/c mice radioprotected with SCID bone marrow, leads to marked engraftment of human T and B cells. In such chimeras, human serum antibody responses can be stimulated readily by vaccination with recall antigens, but the detection of antigen-specific functional T or B cells has been extremely difficult. In the present study, we were able to detect by Elispot analysis high frequencies of immunoglobulin G (IgG)-secreting B cells and mitogen-responsive interferon-gamma (IFN-gamma) or interleukin-4 (IL-4)-secreting T cells in peritoneum and spleen of human/BALB/c chimeric mice during the first 3 weeks after PBMC transfer. Moreover, specific memory responses were elicited by vaccination with tetanus toxoid (TT) or hepatitis B virus (HBV) surface (HBs) antigen of chimeric mice transplanted with PBMC derived from TT- or HBV-immune donors. Substantially higher TT-specific B-cell frequencies were found during the first 3 weeks after vaccination in mice challenged with the specific antigen compared to the levels found in control animals. High numbers of TT-specific IFN-gamma-secreting T cells persisted in the peritoneum of vaccinated, but not of unvaccinated, animals during the entire observation period, but only low numbers of specific IL-4-secreting T cells were found in vaccinated mice. Similar results were achieved following vaccination with HBs antigen of chimeric mice, transplanted with PBMC of HBV immunized donors. Thus, TT or HBsAg-specific antibody responses in our model correlate closely with the existence of specific IFN-gamma-secreting T helper 1/0 cells. Furthermore, these results show that adoptive transfer of human PBMC into lethally irradiated mice provides an efficient approach to generate specific B-cell fusion partners for the production of human monoclonal antibodies and specific T-cell lines for adoptive cell therapy of malignant or infectious diseases.
Keywords: JOURNAL ARTICLE Adoptive Transfer Animal B-Lymphocytes/*IMMUNOLOGY Cytokines/METABOLISM Enzyme-Linked Immunosorbent Assay Epitopes/*IMMUNOLOGY Hepatitis B Surface Antigens/IMMUNOLOGY Human IgG/METABOLISM *Immunization Mice Mice, Inbred BALB C Mice, Inbred NOD Mice, SCID Radiation Chimera/*IMMUNOLOGY Support, Non-U.S. Gov't T-Lymphocytes/*IMMUNOLOGY Tetanus Toxoid/IMMUNOLOGY 991030
A99A0884
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Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.
