Immunotoxicity Testing in Non-Rodent Species

Figures & data

TABLE 1 Leukocyte phenotyping in monkeys and dogs

Cell Types expressing molecule	Molecule	Dog
Pan T-cells	CD2^+	CD5+
Mature T-cells	CD3^+	CD3^+
Helper T-cells	CD3^+/CD4^+	CD3^+/CD4^+
Cytotoxic T-cells	CD3^+/CD8^+	CD3^+/CD8a^+
Pan B-cells	CD3^+/CD20^+	CD21-like or anti-Ig
Natural killer cells	CD3^−/CD16^+	—
Monocytes	CD14^+	—

FIG. 1 Effect of Abatacept on the toral KLH-specific antibody response in monkeys. Cynomolgus monkeys (n = 6 females/group) were immunized with a single 10-mg intramuscular injection of KLH (Pierce) following 10 mg/kg intravenous dose of abatacept [a selective CD80/86 costimulatory inhibitor; CTLA4Ig]. Serum was collected prior to dosing and on post-KLH-immunization Days 8, 15, 22, and 29 and evaluated for total KLH-specific antibodies, Results are expressed as endpoint titer ± SD, defined as the reciprocal of the interpolated dilution equal to 5 times the mean plate background. Abatacept substantially diminished the KLH-specific antibody response (Bigwarfe et al., 2004).

FIG. 2 KLH-specific antibody response in dogs. A single 5- or 10-mg intramuscular injection of KLH (Pacific Biomarine) was administered to ∼17-month old Beagle dogs (n = 2). Serum was collected at 5, 7, 9, 11, 14, 21, and 28 days post-KLH-immunization and evaluated for KLH-specific IgM or IgG antibodies. Results are expressed as EPT, defined as the reciprocal of the interpolated dilution equal to 5 times the mean plate background. A single 5 mg intramuscular dose of KLH was sufficient to produce a robust antibody response in dogs, with a mean peak IgM titer of 12,000 on Day 7 and a mean peak IgG titer of > 119,000 on Day 21 (Bigwarfe et al., 2004).

Bigwarfe T., Abbott M., DeVona D., Gonchoroff D., Haggerty H. G., McAvoy E., Phelps L., Price K., Reilly T. T-cell-dependent antibody responses to keyhole limpet hemocyanin (KLH) in pre-clinical immunotoxicity testing. The Toxicologist/Toxicol. Sci. 2004; 78(S1)429

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