title: T lymphocyte development and function in dogs with X-linked severe combined immunodeficiency.
abstract: Canine X-linked severe combined immunodeficiency disease (XSCID) is characterized by a failure to thrive, thymic dysplasia, and a lack of a T lymphocyte mitogenic response. As in human XSCID, affected dogs in our colony have a mutation in the IL-2R-gamma gene. This mutation dramatically altered T lymphocyte development, because XSCID thymi were severely reduced in size and cellularity, contained an increased proportion of immature CD4-CD8- thymocytes, a decreased proportion of intermediate CD4+CD8+ thymocytes, and a normal proportion of CD4+CD8- and CD4-CD8+ thymocytes. XSCID thymi were also deficient in the percentage of CD3-L+ thymocytes. Interestingly, several XSCID dogs had normal percentages of CD3-L+ PBL. Although the mutation did not interfere with IL-2 production, PHA-activated XSCID PBL demonstrated severely diminished IL-2 binding and were nonresponsive to IL-2. These results indicate that the lack of a functional IL-2R-gamma chain in dogs with XSCID primarily affects developing CD4-CD8- thymocytes as they acquire the cell surface Ag CD3-L and interferes with the ability of peripheral T lymphocytes to bind and respond to IL-2.
authors.affiliation: Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104.
authors.forename: R L
authors.initials: RL
authors.lastname: Somberg
authors.forename: J P
authors.initials: JP
authors.lastname: Robinson
authors.forename: P J
authors.initials: PJ
authors.lastname: Felsburg
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D001854:Bone Marrow Cells; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D004285:Dogs; D005434:Flow Cytometry; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000276:immunology*; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018800:Thy-1 Antigens / Q000096:biosynthesis; D013950:Thymus Gland / Q000166:cytology
chemical_list: D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016827:CD8 Antigens; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D018800:Thy-1 Antigens