title: Postnatal development of T cells in dogs with X-linked severe combined immunodeficiency.
abstract: X-linked severe combined immunodeficiency disease (XSCID) in both humans and dogs results from mutations in the common gamma-chain, gamma c, which is a common component of the receptors for IL-2, IL-4, IL-7, IL-9, and IL-15. Although human and canine XSCID share similar features, such as a failure to thrive, hypogammaglobulinemia, an absent T cell mitogenic response, and thymic dysplasia, near normal percentages of T cells are observed in some affected dogs, whereas XSCID boys have few, if any, circulating T cells. In this study, PBL were analyzed by flow cytometry beginning shortly after birth until 9 wk of age. XSCID dogs < 3 wk of age had an elevated number of B cells and were nearly devoid of T cells, phenotypically resembling most human XSCID patients. At 5 wk of age, however, T cells appeared in approximately one-half of the XSCID dogs, although the absolute number of T cells was one-third of normal in these dogs. While the percentage of CD45RA+ T cells in normal dogs gradually decreased with age from > 90% in neonates to < 40% by 3 to 5 yr of age, in XSCID dogs a rapid decline in the percentage of CD45RA+ T cells was observed, resulting in < 10% CD45RA+ T cells by 7 to 9 wk of age. Maternal engraftment was not detected in any of the XSCID dogs by using a sensitive PCR assay. The appearance of nonmaternally derived T cells in XSCID dogs that undergo a rapid switch from CD45RA+ to CD45RA- suggests that limited thymic emigration and peripheral expansion of T cells can occur in the absence of a functional gamma c.
authors.affiliation: Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Somberg
authors.forename: A
authors.initials: A
authors.lastname: Tipold
authors.forename: B J
authors.initials: BJ
authors.lastname: Hartnett
authors.forename: P F
authors.initials: PF
authors.lastname: Moore
authors.forename: P S
authors.initials: PS
authors.lastname: Henthorn
authors.forename: P J
authors.initials: PJ
authors.lastname: Felsburg
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000276:immunology; D001483:Base Sequence; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008297:Male; D008431:Maternal-Fetal Exchange; D008969:Molecular Sequence Data; D011247:Pregnancy; D016511:Severe Combined Immunodeficiency / Q000276:immunology / Q000662:veterinary*; D013601:T-Lymphocytes / Q000166:cytology*; D014960:X Chromosome
chemical_list: D017931:DNA Primers; D017493:Leukocyte Common Antigens