Beta 2M-/- knockout mice contain low levels of CD8+ cytotoxic T lymphocyte that mediate specific tumor rejection.
C57BL/6 mice with a disrupted beta 2M gene (beta 2M-/- mice) express very low levels of MHC class I molecules and are deficient for CD8+ T lymphocytes. Because CD8+ T cells are thought to be a principle effector cell in tumor rejection, we have assessed the ability of beta 2M-/- mice to respond to tumors. beta 2M-/- knockout mice were challenged with seven independent MHC allogeneic and syngeneic tumors. The beta 2M-/- mice responded very similarly to their CD8+ beta 2M+/- littermates in that they rejected high dose challenges of 4/5 allogeneic tumors and were susceptible to 3/3 syngeneic tumors. In vivo depletion of CD4+ or CD8+ cells from the beta 2M-/- mice resulted in susceptibility to allogeneic tumor. The apparent requirement for CD8+ cells for tumor immunity was corroborated by in vitro assays in which depletion of CD8+ but not CD4+ T cells eliminated tumor-specific CTL activity. mAb blocking studies in which target tumor cells were incubated with MHC class I-specific mAb demonstrated that the tumor-specific CD8+ activity was MHC class I restricted. beta 2M-/- mice therefore contain very small quantities of potent, CD8+ T cells that are capable of rejecting large challenges of allogeneic tumor cells.
Lamousé-Smith
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Department of Biological Sciences, University of Maryland, Baltimore 21228.
Clements
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Ostrand-Rosenberg
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis*; D003602:Cytotoxicity, Immunologic; D006084:Graft Rejection; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D008212:Lymphocyte Depletion; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*; D001613:beta 2-Microglobulin / Q000235:genetics* / Q000502:physiology
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D001613:beta 2-Microglobulin