Phenotype of the accessory cell necessary for mitogen-stimulated T and B cell responses in human peripheral blood: Delineation by its sensitivity to the lysosomotropic agent, L-leucine methyl ester

Dwain L Thiele, M. Kurosaka, P. E. Lipsky

Research output: Contribution to journalArticle

311 Scopus citations

Abstract

The lysosomotropic compound L-leucine methyl ester (Leu-OMe) was utilized to delineate the phenotype of the accessory cells involved in human B and T cell activation in vitro. Leu-OMe was shown to cause lysosomal disruption and selective death of human monocytes (Mφ). After 30-45 minute incubations with this agent, human peripheral blood mononuclear cells (PBM) were nearly completely depleted of Mφ. Associated with this Mφ depletion, PBM were rendered unresponsive to a variety of T and B cell mitogens including the plant lectins phytohemagglutinin, concanavalin A, and pokeweed mitogen as well as the oxidative mitogens sodium periodate and neuraminidase plus galactose oxidase. Leu-OMe mediated loss of responsiveness was the result of a selective loss of an accessory cell necessary for each of these responses since reconstitution was accomplished by the addition of an Mφ-enriched adherent cell population. While intact adherent cells could reconstitute responsiveness, crude Mφ supernatants or highly purified human IL 1 alone were ineffective. Further identification of the Leu-OMe sensitive accessory cell indicated that it was entirely contained within the fraction of the adherent population identified by the monoclonal anti-Mφ antibody, 63D3. The mechanism by which Leu-OMe killed Mφ was dependent on the lysosomal content of these cells, since agents that altered lysosomal enzyme activity such as chloroquine or NH4Cl protected Mφ from Leu-OMe. Thus, the selective killing of Mφ by Leu-OMe appeared to relate to the characteristically rich endowment of lysosomes within these cells. These results support the conclusion that a lysosome-rich, leucine methyl ester-sensitive, intact Mφ identified by the monoclonal anti-Mφ antibody 63D3 is the circulating accessory cell required for mitogen-triggered human B and T cell activation.

Original languageEnglish (US)
Pages (from-to)2282-2290
Number of pages9
JournalJournal of Immunology
Volume131
Issue number5
StatePublished - Dec 1 1983

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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