thymic-factor--circulating and Ataxia-Telangiectasia

Ataxia-telangiectasia (AT) is a complex multiparametric disease associating oculocutaneous telangiectasias, cerebellar ataxia, elevated chromosomal aberration frequency and varied degrees of immunodeficiency. Recently a wasted mutant mouse (wst) has been described as an animal model of AT. We have looked in the wasted mutants for the presence of immune and endocrine abnormalities characteristic of AT. In contrast to the T cell immunodeficiency in AT, wasted mutants had a marked hypoplasia of all lymphoid organs, which affected both T and B lymphocyte subsets. The marked thymic atrophy appearing at the final stage of their disease did not modify the endocrine function of the thymic epithelium which produced normal levels of the thymic hormone thymulin. Although in vitro interleukin 2 (IL-2) production by splenic T cells in response to Con A was markedly diminished, these mice presented normal T and B cell proliferative responses to mitogens. Finally, no significant increase in serum alpha-fetoprotein level (a typical marker of AT) was found throughout the course of the disease. Although by many aspects, i.e. neurological disorder, chromosomal aberrations and early death, wasted mice presented similarities with human AT, major discrepancies in the typical features of immune abnormalities were found between the mouse model and the human disease.

Topics: alpha-Fetoproteins; Animals; Ataxia Telangiectasia; Disease Models, Animal; Female; Interleukin-2; Lymphatic System; Lymphocyte Activation; Lymphocytes; Male; Mice; Mice, Mutant Strains; Mitogens; Spleen; Thymic Factor, Circulating; Thymus Gland

Three children with IgA and IgE deficiency and T-cell defects (two related patients with ataxia telangiectasia and one with common variable immune deficiency) were treated with synthetic serum thymic factor (FTS) intravenously. A reduction in frequency and severity of infection was noted concomitantly with improvement in cell-mediated-immunity tests. Serum IgA, which was absent in two patients, appeared within 4 weeks of treatment and increased significantly in the third patient. Specific antibodies against vaccination antigens appeared for the first time or increased to titres higher than ever before. In two patients, transient interruption of FTS administration was followed by a regression of the immunological improvement, but this disappeared after the treatment was started again.

Topics: Adolescent; Antibody Formation; Ataxia Telangiectasia; Bronchiectasis; Child; Child, Preschool; Dysgammaglobulinemia; Female; Humans; IgA Deficiency; Immunity, Cellular; Immunoglobulin A; Immunoglobulin E; Injections, Intravenous; Male; Thymic Factor, Circulating; Thymus Hormones

Lymphocytes from five children suffering from ataxia telangectasia or various unclassified immune deficiencies were tested in vitro for their sensitivity to synthetic serum thymic factor (FTS). The percentages of cells bearing T cell markers were elevated after incubation with FTS at graded concentrations (0.25, 2.5 and 25 ng/ml), by microlymphocytotoxicity or indirect immunofluorescence, using monoclonal anti-Lyt1 antibodies. In four cases, more than 30% of the non-T non-B cells acquired the Lyt1 T cell marker. These four children had low levels of circulating FTS. In the fifth child, who had a normal serum FTS level, and in two age-matched controls, there was no significant increase in the percentage of cells bearing the T marker.

Topics: Adolescent; Antibodies, Monoclonal; Ataxia Telangiectasia; Child; Child, Preschool; Female; Fluorescent Antibody Technique; Humans; Immunologic Deficiency Syndromes; Leukocyte Count; Male; T-Lymphocytes; Thymic Factor, Circulating; Thymus Hormones