Detectable peripheral T cell populations numbered less than 10(5) cells, and the representation of T subset markers (CD4, CD8) varied widely among individual mice further, Southern blot analysis of TCR gene rearrangements in the DNA of polyclonally stimulated lymphoid cultures from these mice showed very restricted heterogeneity relative to that of cultures from normal mice. By contrast, identifiable T lineage cells in old mice were all CD3+ and predominantly single positive for CD4 or CD8. Most young adult mice contained CD3- populations of CD4/CD8 double positive cells, and in some cases, CD4 or CD8 single positive cells as well. Striking differences in the representation of T cell subsets were seen in the thymus of these two age groups. IgM+ B220+ cells were not detectable in young adult mice (3 mo old), but in old mice (greater than or equal to 1 yr old) they were routinely present in the peritoneal cavity though not in the spleen. The data showed that leaky scid mice are more frequent than is evident from serum Ig analysis and that the incidence of detectable B and T cells increases with age. The configuration of TCR loci in such clones may reflect the ability of the defective scid recombinase to mediate normal rearrangements at a low frequency.Scid mice with and without detectable serum Ig (scid Ig+ and scid Ig- mice, respectively) were examined for the presence of mature 'leaky' lymphocytes by flow microfluorimetry with the use of antibodies to B (IgM, B220) and T (CD3, CD4, CD8) lymphocyte surface Ag. However, one of five leaky T cell clones (S1233) and one Con A stimulated monoclonal culture (8706) contained both normally and abnormally rearranged TCR genes. Establishing diagnostic criteria for severe combined immunodeficiency disease (SCID), leaky SCID, and Omenn syndrome: the Primary Immune Deficiency. This retrospective and cross-sectional study is designed to identify multiple patient, donor, and treatment factors important for survival of children with SCID and SCID-related diseases. Our lead scientists for Leaky SCID research. Shearer WT, Dunn E, Notarangelo LD, et al. In addition to typical SCID, the variant forms of severe primary immunodeficiency 3 studied include leaky SCID, Omenn syndrome, and reticular dysgenesis. San Francisco, California and other locations. Therefore, most leaky lymphocytes appear to derive from progenitors with normal or near-normal scid recombinase activity. Individuals with a past diagnosis of severe combined immune deficiency (including many cases of 'leaky SCID', Omenn syndrome, and reticular dysgenesis) who have undergone blood and marrow transplant, gene therapy, or enzyme replacement in the past.

Four of five alloreactive T cell clones from leaky scid mice also apparently lacked abnormal J-associated deletions in their rearranged TCR alleles. These studies also indicated that TCR gene rearrangements in the majority of the stimulated T cell cultures did not contain abnormal J-associated deletions that are characteristic of antigen receptor genes of scid lymphomas. Indeed, the analysis of TCR gene rearrangements in polyclonally stimulated T cell cultures revealed only 1-5 clones in the pooled spleen and lymph nodes of individual old scid mice. This suggested the presence of very few T cell clones. When CD3+ populations in individual leaky mice were analyzed for expression of the T cell subset markers, CD4 and CD8, the ratios of CD4/CD8 were found to be markedly skewed relative to normal mice.

The number of detectable T cells remained very low individual old scid mice generally contained less than 10(5) CD3+ cells. FACS analysis showed that the incidence of leaky T cells increases with age, such that virtually all old scid mice (greater than 1 year) contain detectable CD3+ cells.

Leaky scid