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Effects of an induced adenosine deaminase deficiency on T-cell differentiation in the rat

Journal Article · · Cell. Immunol.; (United States)
Inherited deficiency of the enzyme adenosine deaminase (ADA) has been found in a significant proportion of patients with severe combined immunodeficiency disease and inherited defect generally characterized by a deficiency of both B and T cells. Two questions are central to understanding the pathophysiology of this disease: (1) at what stage or stages in lymphocyte development are the effects of the enzyme deficiency manifested; (2) what are the biochemical mechanisms responsible for the selective pathogenicity of the lymphoid system. We have examined the stage or stages of rat T-cell development in vivo which are affected by an induced adenosine deaminase deficiency using the ADA inhibitors, erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and 2'-deoxycoformycin (DCF). In normal rats given daily administration of an ADA inhibitor, cortical thymocytes were markedly depleted; peripheral lymphocytes and pluripotent hemopoietic stem cells (CFU-S) all were relatively unaffected. Since a deficiency of ADA affects lymphocyte development, the regeneration of cortical and medullary thymocytes and their precursors after sublethal irradiation was used as a model of lymphoid development. By Day 5 after irradiation the thymus was reduced to 0.10-0.5% of its normal size; whereas at Days 9 and 14 the thymus was 20-40% and 60-80% regenerated, respectively. When irradiated rats were given daily parenteral injections of the ADA inhibitor plus adenosine or deoxyadenosine, thymus regeneration at Days 9 and 14 was markedly inhibited, whereas the regeneration of thymocyte precursors was essentially unaffected. Thymus regeneration was at least 40-fold lower than in rats given adenosine or deoxyadenosine alone. Virtually identical results were obtained with both ADA inhibitors, EHNA and DCF.
Research Organization:
Univ. of Connecticut Health Center, Farmington
OSTI ID:
6168829
Journal Information:
Cell. Immunol.; (United States), Journal Name: Cell. Immunol.; (United States) Vol. 2; ISSN CLIMB
Country of Publication:
United States
Language:
English

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Related Subjects

560152* -- Radiation Effects on Animals-- Animals
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMIDINASES
ANIMAL CELLS
ANIMALS
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BIOLOGICAL RECOVERY
BIOLOGICAL REGENERATION
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CELL DIFFERENTIATION
CHIMERAS
CONNECTIVE TISSUE CELLS
DISEASES
ENZYME INHIBITORS
ENZYMES
HEREDITARY DISEASES
HYDROLASES
IRRADIATION
LEUKOCYTES
LYMPHATIC SYSTEM
LYMPHOCYTES
MAMMALS
MATERIALS
MOSAICISM
NON-PEPTIDE C-N HYDROLASES
ORGANS
PATIENTS
RADIATION CHIMERAS
RATS
RECOVERY
RODENTS
SOMATIC CELLS
SUBLETHAL IRRADIATION
THYMUS
VERTEBRATES