Beta-adrenergic receptors on human suppressor, helper, and cytolytic lymphocytes

doi:10.1016/0006-2952(86)90150-4

Biochemical Pharmacology

Volume 35, Issue 7, 1 April 1986, Pages 1137-1142

https://doi.org/10.1016/0006-2952(86)90150-4 Get rights and content

Abstract

Using the radioligand beta-adrenergic blocker [¹²⁵I]cyanopindolol (ICYP), we have characterized the beta-adrenergic receptors on Leu 3⁺ (T helper [T_H]), Leu 2⁺, 9.3⁻ (T suppressor [T_s]) and Leu 2⁺, 9.3⁺ (T cytolytic [T_c]) subsets of human lymphocytes. Peripheral blood T cells were isolated by rosetting, and then subsets were purified by their affinities to monoclonal antibodies against their Leu 3 and 9.3 markers. ICYP binding to the subsets was saturable with time and with concentration; the binding was stereoselective and reversible by beta-adrenergic antagonists. A biological response produced by beta agonists increased intracellular concentrations of cAMP and corresponded to the number of binding sites. Each subset of cells had a number of binding sites, which was characteristic for the given subset. The data indicate that the density of distribution of beta-adrenergic receptors was not homogeneous on the precursors of phenotypically and functionally distinct T cells (T_s ~ 2900, T_c ~ 1800 and T_H ~ 750 binding sites). The displacement studies using beta-adrenergic agonists were performed on the cytolytic and suppressor T cell subsets, suggesting that the receptors were mainly of the beta-2 type. The immunobiological significance of such selective distribution of numbers and subtypes of betaadrenergic receptors on distinct T cell subsets is under investigation.

References (21)

J.W. Hadden et al.
Cell. Immun
(1970)
E.L. Reinherz et al.
Cell
(1980)
A. Saxon et al.
J. Immun. Meth.
(1976)
R. Pochet et al.
Biochem. Pharmac.
(1983)
M.M. Khan et al.
Clin. Immun. Rev.
(1985)
K.L. Melmon et al.
J. clin. Invest.
(1974)
H.R. Bourne et al.
Science
(1974)
M. Benner et al.
J. Allergy
(1968)
C.S. Henney et al.
J. Immun.
(1972)
J.W. Smith et al.
J. Lab. clin. Med.
(1970)

There are more references available in the full text version of this article.

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^☆: This work was supported by NIH Grants R01 HL 26340, 5R01 CA 24607 and P01 HL 13108.

^§: Present address: Institute di Clinica Medical Generale, Universita degli studi di Parma, Via Gramsci 14, Parma, Italy.

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Beta-adrenergic receptors on human suppressor, helper, and cytolytic lymphocytes☆

Abstract

Cell. Immun

Cell

J. Immun. Meth.

Biochem. Pharmac.

Clin. Immun. Rev.

J. clin. Invest.

Science

J. Allergy

J. Immun.

J. Lab. clin. Med.