Abstract

Mice homozygous for the severe combined immunodeficiency (SCID) mutation lack functional T and B lymphocytes and fail to generate either humoral or cell-mediated immunity. The lack of antigen-specific immunity also allows SCID mice to accept allografts and xenografts. Immune system from several species, including human, rats, cats, cows, horses and pigs, were reconstituted with increasing amount of success into SCID mice. SCID mice models have been used for studying the pathogenesis of some diseases as well as for experimental treatments of diseases like cancer.

Considering that ethical and technical constraints limit the range of experimental immunological studies that can be performed in live cetaceans, there is a need for establishing in vivo models in experimental animals that as closely as possible resemble the cetacean immune system. In a pilot study, SCID mice were reconstituted with 20 x 10⁶ killer whale peripheral blood mononuclear celis (PBMC) or with either 20 x 10⁶ or 100 x 10⁶ splenocytes from a bottlenose dolphin. Mice were sacrificed four weeks after reconstitution and spleen and blood were sampled and analyzed for the presence of dolphin B and T lymphocytes using flow cytometry. Dolphin T lymphocytes were found in spleen from one out of 3 mice reconstituted with 100 x 10⁶ splenocytes and in blood of one out of two mice reconstituted with killer whale PBMC, one out of three mice reconstituted with 20 x 106 splenocytes and in two out of three reconstituted with 100 x 10⁶ splenocytes. Dolphin B lymphocytes were found only in blood from one out of three mice reconstituted with 20 x 10⁶ splenocytes.

Cetacean-reconstituted SCID nice represents an attractive model for the study of the physiology of cetacean immune response as well as the pathophysiology of naturally occurring infectious diseases in captive and wild animals, in addition to represent a unique opportunity to test the efficacy of vaccination programs not only through the production of antigen-specific immunoglobulins but also by testing the level of protection through challenges with the pathogens. A cetacean-SCID model would also allow to address the potential effects of exposure to pollutants on the immune system of cetaceans.