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(American Journal of Pathology. 1999;154:1923-1932.)
© 1999 American Society for Investigative Pathology


Animal Model

A Nonhuman Primate Model for the Selective Elimination of CD8+ Lymphocytes Using a Mouse-Human Chimeric Monoclonal Antibody

Jörn E. Schmitz*, Meredith A. Simon{dagger}, Marcelo J. Kuroda*, Michelle A. Lifton*, Markus W. Ollert{ddagger}, Carl-Wilhelm Vogel{ddagger}, Paul Racz§, Klara Tenner-Racz§, Bernard J. Scallon, Margaret Dalesandro, John Ghrayeb, E. Peter Rieber||, Vito G. Sasseville{dagger} and Keith A. Reimann*

From the Division of Viral Pathogenesis,*
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; the Division of Comparative Pathology,{dagger}
New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts; the Department of Biochemistry and Molecular Biology,{ddagger}
University of Hamburg, Hamburg, Germany; the Bernhard-Nocht-Institute for Tropical Medicine,§

Hamburg, Germany; Centocor, Malvern, Pennsylvania, and the Institute of Immunology,||
Technical University of Dresden, Dresden, Germany

Nonhuman primates provide valuable animal models for human diseases. However, studies assessing the role of cell-mediated immune responses have been difficult to perform in nonhuman primates. We have shown that CD8+ lymphocyte-mediated immunity in rhesus monkeys can be selectively eliminated using the mouse-human chimeric anti-CD8 monoclonal antibody cM-T807. In vitro, this antibody completely blocked antigen-specific expansion of cytotoxic T cells and decreased major histocompatibility complex class I-restricted, antigen-specific lysis of target cells but did not mediate complement-dependent cell lysis. In vivo administration of cM-T807 in rhesus monkeys resulted in near total depletion of CD8+ T cells from the blood and lymph nodes for up to 6 weeks. This depletion was not solely complement-dependent and persisted longer in adults than in juveniles. Preservation of B cell and CD4+ T cell function in monkeys depleted of CD8+ lymphocytes was demonstrated by their ability to develop humoral immune responses to the administered chimeric monoclonal antibody. Furthermore, during CD8+ lymphocyte depletion, monkeys developed delayed-type hypersensitivity reactions comprised only of CD4+ T cells but not CD8+ T cells. This CD8+ lymphocyte depletion model should prove useful in defining the role of cell-mediated immune responses in controlling infectious diseases in nonhuman primates.





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