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. 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.
Schmitz
J E
JE
Division of Viral Pathogenesis, Department of Medicine, Boston, Massachusetts, USA. jschmitz@caregroup.harvard.edu
Simon
M A
MA
Kuroda
M J
MJ
Lifton
M A
MA
Ollert
M W
MW
Vogel
C W
CW
Racz
P
P
Tenner-Racz
K
K
Scallon
B J
BJ
Dalesandro
M
M
Ghrayeb
J
J
Rieber
E P
EP
Sasseville
V G
VG
Reimann
K A
KA
D000818:Animals; D000906:Antibodies / Q000097:blood; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000917:Antibody Formation / Q000187:drug effects; D015703:Antigens, CD / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D003167:Complement Activation / Q000187:drug effects; D004546:Elapid Venoms / Q000494:pharmacology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000097:blood / Q000276:immunology; D007111:Immunity, Cellular / Q000187:drug effects; D008212:Lymphocyte Depletion; D008253:Macaca mulatta; D051379:Mice; D018448:Models, Immunological; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology
D000906:Antibodies; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D004546:Elapid Venoms; D011993:Recombinant Fusion Proteins; D013745:Tetanus Toxoid; C016310:cobra venom factor