Effects of Immunomodulatory Drugs on T Lymphocyte Activation and Function

Abstract

During this second reporting year the following drugs were tested for their immunomodulatory actions: CL246, FK565, OK432, AVS-1300, AVS-2149, and AVS-1761. The drugs were tested for their effects on the proliferative activity of human peripheral blood lymphocytes induced by the mitogenic lectin Concanavalin A (Con A). All of the drugs, except FK565, inhibited lymphocyte proliferation in a dose dependent manner. The potency of inhibition varied among the drugs. We tested whether the inhibition of proliferation was secondary to interfering with the production of the soluble mediators IL1 and IL2 by the drugs. An explanation of the effects of these drugs on lymphocyte proliferation could had been interference with the expression of critical cell surface receptors. To this end, lymphocytes were stimulated with Con A in the presence of drug and the expression of specific receptors was assessed by specific monoclonal antibodies and indirect immunofluorescence. These studies indicate that the above drugs have immunoregulatory effects on human lymphocyte proliferation which can be explained due to secondary effects on the production of IL1 and IL2, as well as, the expression of important cell surface receptors. Finally, of all the drugs, the most remarkable inhibitory effects were displayed by CL246 while the most remarkable potentiating effects were displayed by FK565. Keywords: Immunochemistry, Immunomodulators, Receptor sites, Active sites, Cytotoxic cells.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Jun 15, 1988
Accession Number
ADA199452

Entities

People

  • Constantine D. Tsoukas

Organizations

  • Scripps Research

Tags

DTIC Thesaurus Topics

  • Antibodies
  • Bioassay
  • Blood
  • Cardiovascular System
  • Cell Line
  • Cells
  • Contracts
  • Immune Serums
  • Lymphocytes
  • Molecules
  • Proteins
  • T Lymphocytes
  • Thymidines
  • Thymocytes

Fields of Study

  • Biology
  • Medicine

Readers

  • Child and Adolescent Substance Abuse Science in Autism Spectrum Disorders.
  • Immunology and Pathology
  • Molecular and Cellular Biochemistry