Upregulation of lymphocyte β-adrenergic receptor in Down's syndrome: a biological marker of a neuroimmune deficit

Maria C. Morale, Nunzio Batticane, Matteo Cioni, Bianca Marchetti

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Abstract

To test the hypothesis of an altered central nervous system influence upon the immune system of Down's syndrome (DS) patients and in order to establish a peripheral biological marker of neuroimmune deficit, we have studied the characteristics of the β2-adrenergic receptor (B2AR) system in peripheral blood monocytes (PBMC) of 12 pre-pubertal (six boys and six girls) individuals and correlated alterations in binding with changes in distribution of lymphocyte subsets. Using the very potent β-adrenergic antagonist, iodocyanopindolol ([125I]CYP), as a ligand, the present study shows that a typical BAR population of the β2-subtype is present in PBMC from DS children, with binding kinetics and structural specificity similar to those measured in PBMC from patients with other (non-genetic) forms of mental retardation, or in PBMC from age-matched healthy subjects. On the other hand, this study revealed a significance increase in B2AR binding capacity of PBMC from DS subjects (Bmax = 5258 ± 470 sites/cell) compared to the values measured in the control population of retarded children (Bmax = 1965 ± 280 sites/cell), characterized by an approximately three-fold increase in the Bmax, without changes in binding affinity (KD = 40.5 ± 2.0 and 36.6 ± 2.5 pM in DS and retarded patients, respectively). The flowcytometric markers revealed a profound alteration in the distribution of lymphocyte subtypes with an almost 50% decrease in B cell and T-helper populations, a three-fold increase in T-cytotoxic suppressor, a seven-fold increase in lymphocyte-activated killer cells (LAK) and 30% increase in natural killer (NK) subpopulations. When fluorescence-labelled lymphocytes were visualized in the cytofluorograph and sorted for their use in the radioreceptor assay, B cells had approximately twice the number of B2AR when compared to T cells; and cytotoxic/suppressor showed a higher binding capacity compared to T-helper cells. On the other hand, labelled lymphocytes from DS patients showed a specific increase in receptor number in B cells, T-cytotoxic suppressor and NK subpopulations. It is concluded that a profound catecholaminergic dysfunction not previously appreciated in DS is reflected by a significant alteration in lymphocyte subset distribution and by a specific up-regulation of lymphocyte B2AR in phenotypically and functionally distinct T and B cells as well NK subpopulations, suggesting a possible denervation supersensitivity phenomenon. From the present data it seems tempting to speculate that the B2AR might represent a valuable marker of neuroimmune dysfunction in DS and possibly other brain pathologies.

Original languageEnglish
Pages (from-to)185-198
Number of pages14
JournalJournal of Neuroimmunology
Volume38
Issue number3
DOIs
Publication statusPublished - 1992

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Keywords

  • Cell sorter
  • Down's syndrome
  • Flow cytometry
  • Immune depression
  • Lymphocyte subset
  • Natural killer
  • T-helper
  • T-suppressor
  • β-Adrenergic receptor

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Clinical Neurology
  • Neurology

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