Skip to main content
PMC home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1984 Jul;57(1):220–226.

Lymphocyte subpopulations in Down's syndrome: high percentage of circulating HNK-1+, Leu 2a+ cells.

R Maccario, A G Ugazio, L Nespoli, C Alberini, D Montagna, F Porta, F Bonetti, G R Burgio
PMCID: PMC1536096  PMID: 6235075

Abstract

Peripheral blood lymphomononuclear cells (PBL) from 35 patients with Down's syndrome (DS, trisomy-21; 25 institutionalized and 10 non-institutionalized) were phenotypically characterized by means of various monoclonal antibodies. They included a high percentage of T lymphocytes with low avidity for sheep erythrocytes as well as an extremely high percentage of HNK-1+ cells and of lymphocytes reacting with the OKT8 and Leu 2a antibodies. The HNK-1+ cells of DS include four different subsets: (a) E+, OKT3+, OKT8-, Leu 2a-; (b) E+, OKT3+, OKT8+, Leu 2a+; (c) E-, OKT3-, OKT8-, Leu 2a- and (d) E-, OKT3-, OKT8+, Leu 2a+. Subsets (a) and (c) are also present in PBL from karyotypically normal controls while subsets (b) and (d) have a phenotype which has not been previously reported. These findings may be related to the triple expression by trisomic cells of the receptor for interferon, which is coded by a gene located on chromosome number 21. Alternatively, the high number of 'immature' NK cells of DS, possibly identical with pre-T lymphocytes, may originate from the congenital thymic derangement associated with trisomy 21.

Full text

PDF
222

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abo T., Miller C. A., Gartland G. L., Balch C. M. Differentiation stages of human natural killer cells in lymphoid tissues from fetal to adult life. J Exp Med. 1983 Jan 1;157(1):273–284. doi: 10.1084/jem.157.1.273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. BENDA C. E., STRASSMANN G. S. THE THYMUS IN MONGOLISM. J Ment Defic Res. 1965 Jun;9:109–117. [PubMed] [Google Scholar]
  3. Baxter R. G., Larkins R. G., Martin F. I., Heyma P., Myles K., Ryan L. Down syndrome and thyroid function in adults. Lancet. 1975 Oct 25;2(7939):794–796. doi: 10.1016/s0140-6736(75)80007-9. [DOI] [PubMed] [Google Scholar]
  4. Burgio G. R., Lanzavecchia A., Maccario R., Vitiello A., Plebani A., Ugazio A. G. Immunodeficiency in Down's syndrome: T-lymphocyte subset imbalance in trisomic children. Clin Exp Immunol. 1978 Aug;33(2):298–301. [PMC free article] [PubMed] [Google Scholar]
  5. Burgio G. R., Severi F., Rossoni R., Vaccaro R. Mongolism and thyroid autoimmunity. Lancet. 1965 Jan 16;1(7377):166–167. doi: 10.1016/s0140-6736(65)91125-6. [DOI] [PubMed] [Google Scholar]
  6. Burgio G. R., Ugazio A. G., Nespoli L., Marcioni A. F., Bottelli A. M., Pasquali F. Derangements of immunoglobulin levels, phytohemagglutinin responsiveness and T and B cell markers in Down's syndrome at different ages. Eur J Immunol. 1975 Sep;5(9):600–603. doi: 10.1002/eji.1830050904. [DOI] [PubMed] [Google Scholar]
  7. Duse M., Brugo M. A., Martini A., Tassi C., Ferrario C., Ugazio A. G. Immunodeficiency in Down's syndrome: low levels of serum thymic factor in trisomic children. Thymus. 1980 Dec;2(3):127–131. [PubMed] [Google Scholar]
  8. Epstein L. B., Epstein C. J. T-lymphocyte function and sensitivity to interferon in trisomy 21. Cell Immunol. 1980 May;51(2):303–318. doi: 10.1016/0008-8749(80)90262-2. [DOI] [PubMed] [Google Scholar]
  9. Epstein L. B., Lee S. H., Epstein C. J. Enhanced sensitivity of trisomy 21 monocytes to the maturation-inhibiting effect ot interferon. Cell Immunol. 1980 Mar 1;50(1):191–194. doi: 10.1016/0008-8749(80)90017-9. [DOI] [PubMed] [Google Scholar]
  10. Evans R. L., Wall D. W., Platsoucas C. D., Siegal F. P., Fikrig S. M., Testa C. M., Good R. A. Thymus-dependent membrane antigens in man: inhibition of cell-mediated lympholysis by monoclonal antibodies to TH2 antigen. Proc Natl Acad Sci U S A. 1981 Jan;78(1):544–548. doi: 10.1073/pnas.78.1.544. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fekete G., Kulcsár G., Dán P., Nász I., Schuler D., Dobos M. Immunological and virological investigations in Down's syndrome. Eur J Pediatr. 1982 Feb;138(1):59–62. doi: 10.1007/BF00442331. [DOI] [PubMed] [Google Scholar]
  12. Franceschi C., Licastro F., Paolucci P., Masi M., Cavicchi S., Zannotti M. T and B lypmhocyte subpopulations in Down's syndrome. A study on non-institutionalised subjects. J Ment Defic Res. 1978 Sep;22(3):179–191. doi: 10.1111/j.1365-2788.1978.tb00975.x. [DOI] [PubMed] [Google Scholar]
  13. Gordon M. C., Sinha S. K., Carlson S. D. Antibody responses to influenza vaccine in patients with Down's syndrome. Am J Ment Defic. 1971 Jan;75(4):391–399. [PubMed] [Google Scholar]
  14. Griffiths A. W., Sylvester P. E. Mongols and non-mongols compared in their response to active tetanus immunisation. J Ment Defic Res. 1967 Dec;11(4):263–266. doi: 10.1111/j.1365-2788.1967.tb00229.x. [DOI] [PubMed] [Google Scholar]
  15. Gupta S., Fikrig S. M., Mariano E., Quazi Q. Monoclonal antibody defined T cell subsets and autologous mixed lymphocyte reaction in Down's syndrome. Clin Exp Immunol. 1983 Jul;53(1):25–30. [PMC free article] [PubMed] [Google Scholar]
  16. Handzel Z. T., Dolfin Z., Levin S., Altman Y., Hahn T., Trainin N., Gadot N. Effect of thymic humoral factor on cellular immune factors of normal children and of pediatric patients with ataxia telangiectasia and Down's syndrome. Pediatr Res. 1979 Jul;13(7):803–806. doi: 10.1203/00006450-197907000-00002. [DOI] [PubMed] [Google Scholar]
  17. Henle G., Henle W. Epstein-Barr virus-specific IgA serum antibodies as an outstanding feature of nasopharyngeal carcinoma. Int J Cancer. 1976 Jan 15;17(1):1–7. doi: 10.1002/ijc.2910170102. [DOI] [PubMed] [Google Scholar]
  18. Herberman R. B., Holden H. T. Natural cell-mediated immunity. Adv Cancer Res. 1978;27:305–377. doi: 10.1016/s0065-230x(08)60936-7. [DOI] [PubMed] [Google Scholar]
  19. Indiveri F., Pellegrino M. A., Molinaro G. A., Quaranta V., Ferrone S. Rosetting of human T lymphocytes with goat red blood cells: effect of treatment with 2-aminoethylisothiouronium bromide (AET) and comparison with AET treated sheep red blood cells. J Immunol Methods. 1979;30(4):317–328. doi: 10.1016/0022-1759(79)90014-0. [DOI] [PubMed] [Google Scholar]
  20. KRIVIT W., GOOD R. A. Simultaneous occurrence of mongolism and leukemia; report of a nationwide survey. AMA J Dis Child. 1957 Sep;94(3):289–293. doi: 10.1001/archpedi.1957.04030040075012. [DOI] [PubMed] [Google Scholar]
  21. Levin S., Nir E., Mogilner B. M. T system immune-deficiency in Down's syndrome. Pediatrics. 1975 Jul;56(1):123–126. [PubMed] [Google Scholar]
  22. Levin S., Schlesinger M., Handzel Z., Hahn T., Altman Y., Czernobilsky B., Boss J. Thymic deficiency in Down's syndrome. Pediatrics. 1979 Jan;63(1):80–87. [PubMed] [Google Scholar]
  23. London J., Berrih S., Bach J. F. Peanut agglutinin. I. A new tool for studying T lymphocyte subpopulations. J Immunol. 1978 Aug;121(2):438–443. [PubMed] [Google Scholar]
  24. Lopez V., Ochs H. D., Thuline H. C., Davis S. D., Wedgwood R. J. Defective antibody response to bacteriophage phichi 174 in Down syndrome. J Pediatr. 1975 Feb;86(2):207–211. doi: 10.1016/s0022-3476(75)80469-0. [DOI] [PubMed] [Google Scholar]
  25. Maccario R., Nespoli L., Mingrat G., Vitiello A., Ugazio A. G., Burgio G. R. Lymphocyte subpopulations in the neonate: identification of an immature subset of OKT8-positive, OKT3-negative cells. J Immunol. 1983 Mar;130(3):1129–1131. [PubMed] [Google Scholar]
  26. Minato N., Bloom B. R., Jones C., Holland J., Reid L. M. Mechanism of rejection of virus persistently infected tumor cells by athymic nude mice. J Exp Med. 1979 May 1;149(5):1117–1133. doi: 10.1084/jem.149.5.1117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Mogensen K. E., Vignaux F., Gresser I. Enhanced expression of cellular receptors for human interferon alpha on peripheral lymphocytes from patients with Down's syndrome. FEBS Lett. 1982 Apr 19;140(2):285–287. doi: 10.1016/0014-5793(82)80915-0. [DOI] [PubMed] [Google Scholar]
  28. Nespoli L., Vitiello A., Maccario R., Lanzavecchia A., Ugazio A. G. Activation of human peripheral blood lymphocytes: effect of concanavalin A and lipopolysaccharide on in vitro synthesis of DNA and immunoglobulins. Scand J Immunol. 1980;12(2):165–170. doi: 10.1111/j.1365-3083.1980.tb00054.x. [DOI] [PubMed] [Google Scholar]
  29. Nurmi T., Huttunen K., Lassila O., Henttonen M., Säkkinen A., Linna S. L., Tiilikainen A. Natural killer cell function in trisomy-21 (Down's syndrome). Clin Exp Immunol. 1982 Mar;47(3):735–741. [PMC free article] [PubMed] [Google Scholar]
  30. Oster J., Mikkelsen M., Nielsen A. Mortality and life-table in Down's syndrome. Acta Paediatr Scand. 1975 Mar;64(2):322–326. doi: 10.1111/j.1651-2227.1975.tb03842.x. [DOI] [PubMed] [Google Scholar]
  31. Perussia B., Acuto O., Terhorst C., Faust J., Lazarus R., Fanning V., Trinchieri G. Human natural killer cells analyzed by B73.1, a monoclonal antibody blocking Fc receptor functions. II. Studies of B73.1 antibody-antigen interaction on the lymphocyte membrane. J Immunol. 1983 May;130(5):2142–2148. [PubMed] [Google Scholar]
  32. Perussia B., Starr S., Abraham S., Fanning V., Trinchieri G. Human natural killer cells analyzed by B73.1, a monoclonal antibody blocking Fc receptor functions. I. Characterization of the lymphocyte subset reactive with B73.1. J Immunol. 1983 May;130(5):2133–2141. [PubMed] [Google Scholar]
  33. Reinherz E. L., Kung P. C., Goldstein G., Schlossman S. F. A monoclonal antibody reactive with the human cytotoxic/suppressor T cell subset previously defined by a heteroantiserum termed TH2. J Immunol. 1980 Mar;124(3):1301–1307. [PubMed] [Google Scholar]
  34. Reinherz E. L., Kung P. C., Goldstein G., Schlossman S. F. Separation of functional subsets of human T cells by a monoclonal antibody. Proc Natl Acad Sci U S A. 1979 Aug;76(8):4061–4065. doi: 10.1073/pnas.76.8.4061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Reinherz E. L., Penta A. C., Hussey R. E., Schlossman S. F. A rapid method for separating functionally intact human T lymphocytes with monoclonal antibodies. Clin Immunol Immunopathol. 1981 Nov;21(2):257–266. doi: 10.1016/0090-1229(81)90214-2. [DOI] [PubMed] [Google Scholar]
  36. Reisner Y., Biniaminov M., Rosenthal E., Sharon N., Ramot B. Interaction of peanut agglutinin with normal human lymphocytes and with leukemic cells. Proc Natl Acad Sci U S A. 1979 Jan;76(1):447–451. doi: 10.1073/pnas.76.1.447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Roder J. C., Karre K., Kiessling R. Natural killer cells. Prog Allergy. 1981;28:66–159. [PubMed] [Google Scholar]
  38. Tan U. H. Chromosome-21-dosage effect on inducibility of anti-viral gene(s). Nature. 1975 Jan 24;253(5489):280–282. doi: 10.1038/253280a0. [DOI] [PubMed] [Google Scholar]
  39. Targan S., Dorey F. Interferon activation of "pre-spontaneous killer" (pre-SK) cells and alteration in kinetics of lysis of both "pre-SK" and active SK cells. J Immunol. 1980 May;124(5):2157–2161. [PubMed] [Google Scholar]
  40. Trinchieri G., Santoli D. Anti-viral activity induced by culturing lymphocytes with tumor-derived or virus-transformed cells. Enhancement of human natural killer cell activity by interferon and antagonistic inhibition of susceptibility of target cells to lysis. J Exp Med. 1978 May 1;147(5):1314–1333. doi: 10.1084/jem.147.5.1314. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Ugazio A. G., Jayakar S. D., Marcioni A. F., Duse M., Monafo V., Pasquali F., Burgio G. R. Immunodeficiency in Down's syndrome: relationship between presence of human thyroglobulin antibodies and HBsAg carrier status. Eur J Pediatr. 1977 Oct 12;126(3):139–146. doi: 10.1007/BF00442195. [DOI] [PubMed] [Google Scholar]
  42. Ugazio A. G., Lanzavecchia A., Jayakar S., Plebani A., Duse M., Burgio G. R. Immunodeficiency in Down's syndrome. Titres of "natural" antibodies to E. coli and rabbit erythrocytes at different ages. Acta Paediatr Scand. 1978 Nov;67(6):705–708. doi: 10.1111/j.1651-2227.1978.tb16247.x. [DOI] [PubMed] [Google Scholar]
  43. Warner N. L., Woodruff M. F., Burton R. C. Inhibition of the growth of lymphoid tumours in syngeneic athymic (nude) mice. Int J Cancer. 1977 Jul 15;20(1):146–155. doi: 10.1002/ijc.2910200122. [DOI] [PubMed] [Google Scholar]
  44. West W. H., Boozer R. B., Herberman R. B. Low affinity E-rosette formation by the human K cell. J Immunol. 1978 Jan;120(1):90–95. [PubMed] [Google Scholar]
  45. Whittingham S., Pitt D. B., Sharma D. L., Mackay I. R. Stress deficiency of the T-lymphocyte system exemplified by Down syndrome. Lancet. 1977 Jan 22;1(8004):163–166. doi: 10.1016/s0140-6736(77)91763-9. [DOI] [PubMed] [Google Scholar]
  46. Wysocki L. J., Sato V. L. "Panning" for lymphocytes: a method for cell selection. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2844–2848. doi: 10.1073/pnas.75.6.2844. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES