DNA Polymerase Activity As an Index of Lymphocyte Stimulation: Studies in Down's Syndrome

Overview

Journal J Clin Invest

Specialty General Medicine

Date 1970 Jan 1

PMID 4188267

Citations 17

Authors

S S Agarwal

B S Blumberg

B J Gerstley

W T London

A I Sutnick

L A Loeb

Affiliations

Soon will be listed here.

Abstract

The ability of peripheral blood lymphocytes to respond to phytohemagglutinin (PHA) in vitro was studied in patients with Down's syndrome. The response was measured by the increase in DNA polymerase activity and the rate of incorporation of tritiated thymidine by the cultured lymphocytes. These activities were significantly lower in PHA-stimulated lymphocytes from patients with Down's syndrome compared with age- and sex-matched, mentally retarded patients without Down's syndrome from the same institution and the normal healthy volunteers. The impairment in response to PHA does not seem to be related to the presence of Australia antigen in patients with Down's syndrome or to institutionalization itself. In contrast to DNA polymerase activity and thymidine-(3)H uptake, there was no significant difference in the percentage of blast transformation in the three groups studied. The poor response of the lymphocytes from patients with Down's syndrome to a mitogenic stimulus could reflect an impairment of cellular immune functions in these patients which may be one of the factors contributing to the vulnerability of these patients to repeated or persistent infections.

Citing Articles

Cellular Senescence in Neurodegenerative Diseases.

Martinez-Cue C, Rueda N Front Cell Neurosci. 2020; 14:16.

PMID: 32116562 PMC: 7026683. DOI: 10.3389/fncel.2020.00016.

Loss of DNA polymerase β induces cellular senescence.

Ahmed A, Smoczer C, Pace B, Patterson D, Cress Cabelof D Environ Mol Mutagen. 2018; 59(7):603-612.

PMID: 29968395 PMC: 6203593. DOI: 10.1002/em.22206.

Mutational spectrum at GATA1 provides insights into mutagenesis and leukemogenesis in Down syndrome.

Cabelof D, Patel H, Chen Q, Van Remmen H, Matherly L, Ge Y Blood. 2009; 114(13):2753-63.

PMID: 19633202 PMC: 2756130. DOI: 10.1182/blood-2008-11-190330.

Intrinsic defect of the immune system in children with Down syndrome: a review.

Kusters M, Verstegen R, Gemen E, de Vries E Clin Exp Immunol. 2009; 156(2):189-93.

PMID: 19250275 PMC: 2759463. DOI: 10.1111/j.1365-2249.2009.03890.x.

Immunological and virological investigations in Down's syndrome.

Fekete G, Kulcsar G, Dan P, Nasz I, Schuler D, Dobos M Eur J Pediatr. 1982; 138(1):59-62.

PMID: 6281021 DOI: 10.1007/BF00442331.

References

Greene E, Shenker I, KARELITZ S . Serum protein fractions in patients with Down's syndrome (mongolism). Am J Dis Child. 1968; 115(5):599-602. DOI: 10.1001/archpedi.1968.02100010601010. View

Kamin R, Fudenberg H, Douglas S . A genetic defect in "acquired" agammaglobulinemia. Proc Natl Acad Sci U S A. 1968; 60(3):881-5. PMC: 225134. DOI: 10.1073/pnas.60.3.881. View

HUNGERFORD D . Leukocytes cultured from small inocula of whole blood and the preparation of metaphase chromosomes by treatment with hypotonic KCl. Stain Technol. 1965; 40(6):333-8. DOI: 10.3109/10520296509116440. View

ROBBINS J . TISSUE CULTURE STUDIES OF THE HUMAN LYMPHOCYTE. Science. 1964; 146(3652):1648-54. DOI: 10.1126/science.146.3652.1648. View

Stiehm E, Fudenberg H . Serum levels of immune globulins in health and disease: a survey. Pediatrics. 1966; 37(5):715-27. View

Hayakawa H, Matsui I, Higurashi M, Kobayashi N . Hyperblastic response to dilute P.H.A. in Down's syndrome. Lancet. 1968; 1(7533):95-6. DOI: 10.1016/s0140-6736(68)90109-8. View

Miller D . The immunologic capability of patients with lymphoma. Cancer Res. 1968; 28(7):1441-8. View

Olson G, DENT P, Rawls W, South M, Montgomery J, Melnick J . Abnormalities of in vitro lymphocyte responses during rubella virus infections. J Exp Med. 1968; 128(1):47-68. PMC: 2138505. DOI: 10.1084/jem.128.1.47. View

SOUTHAM C . The immunologic status of patients with nonlymphomatous cancer. Cancer Res. 1968; 28(7):1433-40. View

10.

Wheelock E . Interferon-Like Virus-Inhibitor Induced in Human Leukocytes by Phytohemagglutinin. Science. 1965; 149(3681):310-1. DOI: 10.1126/science.149.3681.310. View

11.

Loeb L . Purification and properties of deoxyribonucleic acid polymerase from nuclei of sea urchin embryos. J Biol Chem. 1969; 244(7):1672-81. View

12.

Burgio G, Severi F, ROSSONI R, Vaccaro R . Mongolism and thyroid autoimmunity. Lancet. 1965; 1(7377):166-7. DOI: 10.1016/s0140-6736(65)91125-6. View

13.

Willems F, Melnick J, Rawls W . Viral inhibition of the phytohemagglutinin response of human lymphocytes and application to viral hepatitis. Proc Soc Exp Biol Med. 1969; 130(2):652-61. DOI: 10.3181/00379727-130-33628. View

14.

Hirschhorn K, Bach F, KOLODNY R, FIRSCHEIN I, Hashem N . IMMUNE RESPONSE AND MITOSIS OF HUMAN PERIPHERAL BLOOD LYMPHOCYTES IN VITRO. Science. 1963; 142(3596):1185-7. DOI: 10.1126/science.142.3596.1185. View

15.

Loeb L, Agarwal S, Woodside A . Induction of DNA polymerase in human lymphocytes by phytohemagglutinin. Proc Natl Acad Sci U S A. 1968; 61(3):827-34. PMC: 305402. DOI: 10.1073/pnas.61.3.827. View

16.

SIMONS M, Fowler R, Fitzgerald M . Mechanism of lymphocyte transformation induced by phytohaemagglutinin. Nature. 1968; 219(5158):1021-5. DOI: 10.1038/2191021a0. View

17.

Oppenheim J . Relationship of in vitro lymphocyte transformation to delayed hypersensitivity in guinea pigs and man. Fed Proc. 1968; 27(1):21-8. View

18.

Griffiths A, SYLVESTER P . Mongols and non-mongols compared in their response to active tetanus immunisation. J Ment Defic Res. 1967; 11(4):263-6. DOI: 10.1111/j.1365-2788.1967.tb00229.x. View

19.

FORBES I . SPECIFIC AND NON-SPECIFIC STIMULATION OF ANTIBODY SYNTHESIS BY HUMAN LEUCOCYTES IN VITRO. Lancet. 1965; 1(7378):198-9. DOI: 10.1016/s0140-6736(65)90979-7. View

20.

PEARMAIN G, LYCETTE R, Fitzgerald P . Tuberculin-induced mitosis in peripheral blood leucocytes. Lancet. 1963; 1(7282):637-8. DOI: 10.1016/s0140-6736(63)91275-3. View