Essentials for starting a pediatric clinical study (3): Dynamic changes in early development of immune system in macaque monkeys--the significance from standpoint of preclinical toxicity test using nonhuman primates.
Macaque monkeys are essential laboratory animals in preclinical safety assessment for human-specific biological products including humanized antibody drug. In most case, investigators are leaving their ages out of consideration, and young individuals aged around 3 years are mainly used because of their small individual differences in biological responses to various stimulations. Since the immune system starts to develop just after birth and remarkable phenotypic and functional changes occur in various kinds of immunocompetent cells during the first few years of life in macaque monkeys, their actual immunological condition must be carefully considered in case of safety assessment of novel drugs which modulate human immune function. The early development of major immune functions of macaque monkeys is summarized as follows. These findings suggest that immunocompetent cells drastically differentiate into activated ones during early development. 1) The serum immunoglobulin contents gradually rise with increasing age up to sexual maturity. 2) The blood group-associated antibodies, anti-A and anti-B antibody, are detected around 40-days of age and antibody levels rapidly increase after one year old. 3) Infant cynomolgus monkeys obviously produce the significant levels of IgG antibody against Campylobacter jejuni within 4 weeks after infection when maternal antibody becomes undetectable (8 weeks of age). 4) The frequency of lymphocyte subpopulations expressing the resting surface phenotypes is much higher than that having activated phenotypes in neonates, and the relative population of lymphocyte subsets with resting phenotype decrease with increasing age, while the subpopulation associated with activation gradually increase with age.
Terao
Keiji
K
Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Ibaragi, Japan. terao@nibio.go.jp
D000818:Animals; D000906:Antibodies / Q000097:blood; D001789:Blood Group Antigens / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D016123:Campylobacter jejuni / Q000276:immunology; D007074:Immunoglobulin G; D007136:Immunoglobulins / Q000097:blood; D016131:Lymphocyte Subsets / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D008251:Macaca / Q000276:immunology*; D010641:Phenotype; D018675:Toxicity Tests
D000906:Antibodies; D001789:Blood Group Antigens; D018106:CD28 Antigens; D017252:CD3 Complex; D007074:Immunoglobulin G; D007136:Immunoglobulins