The effect of 1-chloro-2,4-dinitrobenzene exposure on antigen receptor (CD3)-stimulated transmembrane signal transduction in purified subsets of human peripheral blood lymphocytes.
The intracellular low-molecular-weight thiol glutathione (GSH) is an important scavenger of free radicals and plays a role in the maintenance of the redox status of protein sulfhydryl groups. We have previously shown that human peripheral blood lymphocytes sorted on their basal GSH content proliferate proportionately to their GSH levels, and that an early event in lymphocyte activation appeared to be dependent on GSH. We have now analyzed transmembrane signal transduction in cells treated with 1-chloro-2,4-dinitrobenzene (CDNB), a GSH-depleting agent. Transmembrane signal transduction was measured as changes in intracellular free calcium and in protein tyrosine phosphorylation after stimulation with anti-CD3 monoclonal antibody. The results show a CDNB dose-dependent reduction in GSH content, the magnitude of intracellular free calcium mobilization, and the extent of tyrosine phosphorylation of several proteins, including phospholipase C-gamma 1. This suggests a role for GSH and/or protein thiol redox status in one of the earliest events controlling the ability of lymphocytes to respond to important proliferative signals in their environment and implies that agents which deplete lymphocyte GSH may be immunosuppressive through effects on CD3/T cell receptor-dependent transmembrane signal transduction.
Kavanagh
T J
TJ
Department of Medicine, University of Washington, Seattle 98195.
Grossmann
A
A
Jinneman
J C
JC
Kanner
S B
SB
White
C C
CC
Eaton
D L
DL
Ledbetter
J A
JA
Rabinovitch
P S
PS
D000911:Antibodies, Monoclonal; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004137:Dinitrochlorobenzene / Q000633:toxicity*; D005434:Flow Cytometry; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D011506:Proteins / Q000378:metabolism; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D000911:Antibodies, Monoclonal; D004137:Dinitrochlorobenzene; D011506:Proteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D014443:Tyrosine; D005978:Glutathione; D002118:Calcium