POSTNATAL-DEVELOPMENT OF T-CELLS IN DOGS WITH X-LINKED SEVERE COMBINED IMMUNODEFICIENCY

X-linked severe combined immunodeficiency disease (XSCID) in both huma ns 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 flo w cytometry beginning shortly after birth until 9 wk of age. XSCID dog s <3 wk of age had an elevated number of B cells and were nearly devoi d of T cells, phenotypically resembling most human XSCID patients, At 5 wk of age, however, T cells appeared in approximately one-half of th e 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 no rmal dogs gradually decreased with age from >90% in neonates to <40% b y 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 b y 7 to 9 wk of age. Maternal engraftment was not detected in any of th e XSCID dogs by using a sensitive PCR assay. The appearance of nonmate rnally derived T cells in XSCID dogs that undergo a rapid switch from CD45RA(+) to CD45RA(-) suggests that limited thymic emigration and per ipheral expansion of T cells can occur in the absence of a functional gamma c.