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

Nonhuman primates provide valuable animal models for human diseases. Howeve r, studies assessing the role of cell-mediated immune responses have been d ifficult to perform in nonhuman primates, We have shown that CD8+ lymphocyt e-mediated immunity in rhesus monkeys can be selectively eliminated using t he mouse-human chimeric anti-CDS monoclonal antibody cM-T807, In vitro, thi s antibody completely blocked antigen-specific expansion of cytotoxic T cel ls and decreased major histocompatibility complex class I-restricted, antig en-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 persist ed longer in adults than in juveniles, Preservation of B cell and CD4+ T ce ll function in monkeys depleted of CD8+ lymphocytes was demonstrated by the ir ability to develop humoral immune responses to the administered chimeric mono-clonal antibody. Furthermore, during CD8+ lymphocyte depletion, monke ys 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 cont roling infectious diseases in nonhuman primates.