A nonhuman primate model for the selective elimination of CD8+ lymphocytes using a mouse-human chimeric monoclonal antibody

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

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

107 Citations (Scopus)

Abstract

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. Presentation 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.

Original languageEnglish
Pages (from-to)1923-1932
Number of pages10
JournalAmerican Journal of Pathology
Volume154
Issue number6
DOIs
Publication statusPublished - Jun 1999
Externally publishedYes

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