Gallium arsenide selectively inhibits T cell proliferation and alters expression of CD25 (IL-2R/p55)

J Pharmacol Exp Ther. 1993 Apr;265(1):178-86.

Abstract

Exposure (24 hr) to a single intratracheal administration of gallium arsenide (GaAs; 200 mg/kg) has been shown to suppress antibody production as well as other T cell-mediated immunological functions. GaAs has also been shown to exert toxic effects on events occurring early in the antibody-forming cell response which may include lymphocyte activation and proliferation. Studies were undertaken to determine whether GaAs exposure resulted in the inability of T and B lymphocytes to proliferate in response to an antigenic stimulus. During the first 24 hr after in vitro immunization with sheep red blood cells, GaAs-exposed splenocytes were suppressed 51% in their ability to proliferate compared to the vehicle (0.05% Tween 80 in saline; VH) control. There was no significant difference in absolute numbers of cluster designation (CD)8+ cells between VH- and GaAs-exposed cultures. There was, however, a 50% decrease in CD4+ cells evaluated 24 hr after immunization with sheep red blood cells which persisted for the 5-day culture period. T and B cells were isolated and analyzed for proliferative capacity in response to various mitogenic stimuli. Isolated B cells exhibited no difference between VH- and GaAs-exposed cells in proliferative capacity to either lipopolysaccharide or anti-immunoglobulin plus interleukin-4. However, isolated T cells exposed to GaAs were significantly suppressed in their ability to proliferate to concanavalin A, phytohemagglutinin and anti-CD3 epsilon plus interleukin-2 when compared to VH. In addition, expression of CD25, leukocyte function antigen-1 and intercellular adhesion molecule-1 in GaAs-exposed mice were significantly below VH (36, 18 and 18%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arsenic / toxicity*
  • Arsenicals*
  • B-Lymphocytes / cytology
  • B-Lymphocytes / drug effects
  • Cell Adhesion Molecules / metabolism
  • Cell Division / drug effects
  • Cells, Cultured
  • Female
  • Gallium / toxicity*
  • Intercellular Adhesion Molecule-1
  • Lymphocyte Function-Associated Antigen-1 / metabolism
  • Mice
  • Mitogens / pharmacology
  • Receptors, Interleukin-2 / biosynthesis*
  • Spleen / cytology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / metabolism

Substances

  • Arsenicals
  • Cell Adhesion Molecules
  • Lymphocyte Function-Associated Antigen-1
  • Mitogens
  • Receptors, Interleukin-2
  • Intercellular Adhesion Molecule-1
  • gallium arsenide
  • Gallium
  • Arsenic