Limitation of Hu-PBL-scid mouse model in direct application to immunotoxicity assessment

Abstract

Hu-PBC-scid mice were directly introduced to the methods of immunotoxicity assessments. Human IgG and IgM was detected 1 week after transplantation. Cyclosporin A (CsA) and cyclophosphamide (CP), which were injected i.p. 4 weeks after transplantation, decreased the serum concentration of IgM after 2-4 days of treatment but not that of IgG. Lymphocyte proliferation induced by various mitogens and primary T-dependent antibody responses to sheep red blood cells could not be measured by using splenocytes of hu-PBL-scid mice. These results were correlated with the fact that human cells were not detected in the spleen, thymus, or blood of hu-PBL-scid mouse but were detected in lymph nodes of the intestine, which were observed by flow cytometric and immunohistochemical examinations. The present results suggest using hu-PBL-scid mice in routine immunotoxicity investigations; lymph nodes of intestines could be used as the lymphocyte sources. In addition, the determination of serum Ig concentration might be used as a experimental item.