Generation of primary antigen-specific human cytotoxic T lymphocytes in human/mouse radiation chimera. NLM AIDSLINE Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.

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Generation of primary antigen-specific human cytotoxic T lymphocytes in human/mouse radiation chimera.

Blood. 1996 Jul 15;88(2):721-30. Unique Identifier : AIDSLINE MED/96289522
Segall H; Lubin I; Marcus H; Canaan A; Reisner Y; Department of Membrane Research and Biophysics, Weizmann; Institute of Science, Rehovot, Israel.

Abstract: Severe combined immunodeficient (SCID) mice are increasingly used as hosts for the adoptive transfer of human lymphocytes. Human antibody responses can be obtained in these xenogeneic chimeras, but information about the functionality of the human T cells in SCID mice is limited and controversial. Studies using human peripheral blood lymphocytes (PBL) injected intraperitoneally (IP) into SCID mice (hu-PBL-SCID mice) have shown that human T cells from these chimeras are anergic and have a defective signaling via the T-cell receptor. In addition, their antigenic repertoire is limited to xenoreactive clones. In the present study, we tested the functionality of human T cell in a recently described chimeric model. In this system, BALB/c mice are conditioned by irradiation and then transplanted with SCID bone marrow, followed by IP injection of human PBL. Our experiments demonstrated that human T cells, recovered from these hu-PBL-BALB mice within 1 month posttransplant, proliferated and expressed activation markers upon stimulation with anti-CD3 monoclonal antibody. A vigorous antiallogeneic human cytotoxic T-lymphocyte (CTL) response could be generated in these mice by immunizing them with irradiated allogeneic cells. Moreover, anti-human immunodeficiency virus type 1 (HIV-1) Net-specific human CTLs could be generated in vivo from naive lymphocytes by immunization of mouse-human chimeras with a recombinant vaccinia-nef virus. This model may be used to evaluate potential immunomodulatory drugs or cytokines, and could provide a relevant model for testing HIV vaccines, for production of antiviral T-cell clones for adoptive therapy, and for studying human T-cell responses in vivo.
Keywords: Animal AIDS Vaccines/IMMUNOLOGY Bone Marrow Transplantation Burkitt's Lymphoma/IMMUNOLOGY/PATHOLOGY Cytotoxicity, Immunologic Gene Products, nef/*IMMUNOLOGY Graft Rejection/IMMUNOLOGY Human HIV-1/*IMMUNOLOGY Immunization Immunotherapy, Adoptive Injections, Intraperitoneal Isoantigens/*IMMUNOLOGY Lymphocyte Transformation Mice Mice, Inbred BALB C Mice, SCID/*IMMUNOLOGY Muromonab-CD3/IMMUNOLOGY Neoplasm Transplantation/IMMUNOLOGY Radiation Chimera/*IMMUNOLOGY Receptors, Interleukin-2/ANALYSIS Support, Non-U.S. Gov't T-Lymphocytes/*TRANSPLANTATION T-Lymphocytes, Cytotoxic/*IMMUNOLOGY Transplantation, Heterologous/*IMMUNOLOGY Transplantation, Homologous Tumor Cells, Cultured Vaccines, Synthetic/IMMUNOLOGY Vaccinia Virus/IMMUNOLOGY JOURNAL ARTICLEKWDanimalaidsvaccines/immunologybonemarrowtransplantationburkitt'slymphoma/immunology/pathologycytotoxicity,immunologicgeneproducts,nef/KWDimmunologygraftrejection/immunologyhumanhiv-1/KWDimmunologyimmunizationimmunotherapy,adoptiveinjections,intraperitonealisoantigens/KWDimmunologylymphocytetransformationmicemice,inbredbalbcmice,scid/KWDimmunologymuromonab-cd3/immunologyneoplasmtransplantation/immunologyradiationchimera/KWDimmunologyreceptors,interleukin-2/analysissupport,non-uKWDsKWDgov'tt-lymphocytes/KWDtransplantationt-lymphocytes,cytotoxic/KWDimmunologytransplantation,heterologous/KWDimmunologytransplantation,homologoustumorcells,culturedvaccines,synthetic/immunologyvacciniavirus/immunologyjournalarticle
961130
M96B1873

Copyright © 1996 - National Library of Medicine. Reproduced under license with the National Library of Medicine, Bethesda, MD.

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