Gnotobiotics and immunopathology: the use of the gnotobiotic environment to study acquired and inherited immunodeficiency diseases.

Abstract

Gnotobiotic animals are highly valued for the study of infectious diseases wherein the clinical signs and lesions of disease can be directly related to host-pathogen interactions and not to the additive effects of environmental influences and other confounding factors. Gnotobiotic dogs have been used to study the pathogenesis of acquired immunodeficiencies associated with canine distemper virus (CDV). In recent years, the laboratory at OSU, in conjunction with University of Pennsylvania personnel have begun a series of long-term studies of dogs affected with the canine X chromosome-linked severe combined immunodeficiency (XSCID) syndrome. This fatal inherited defect is caused by mutation in the common gamma chain (IL2RG) gene and renders affected animals profoundly immunodeficient. XSCIDs dogs, raised within a gnotobiotic environment for up to 3 years remain clinically healthy and are, in every respect normal except for the persistent T-cell defect and the failure to develop lymph nodes. Bone marrow transplantation (unfractionated or enriched for CD34+ stem cells) is the treatment of choice for both the XSCID dogs and male human infants affected with this syndrome. In preliminary studies, we have shown that human CD34+ stem cells colonized XSCIDs-affected gnotobiotic dogs, migrated to the thymus and demonstrated post-thymic activation (CD45RA+ phenotype) in peripheral blood. While many issues are unresolved, these data suggest that, through the use of the gnotobiotic environment, xenotransplantation (human-to-dog) may yield a stable and immunologically functional human-dog chimera.

• Authors: Steven Krakowka, Peter Felsburg
• Journal: Veterinary immunology and immunopathology (Vet Immunol Immunopathol) Vol. 108 Issue 1-2 Pg. 165-75 (Oct 18 2005) ISSN: 0165-2427 [Print] Netherlands
• PMID: 16112740 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Topics

• Animals
• Bone Marrow Transplantation
• Chimera (immunology)
• Disease Models, Animal
• Dog Diseases (genetics, immunology, pathology)
• Dogs
• Genetic Diseases, X-Linked (genetics, immunology, pathology, veterinary)
• Germ-Free Life (immunology)
• Humans
• Immunologic Deficiency Syndromes (immunology, pathology, therapy)
• Infant
• Male
• Severe Combined Immunodeficiency (genetics, immunology, pathology, veterinary)