Bacterial toxins affect early events of T lymphocyte activation.
The effects of pertussis toxin and cholera toxin on early events of T lymphocyte activation were examined in the T lymphocyte cell line, Jurkat. Pertussis toxin treatment of these T cells increased inositol phosphates production and led to increases in intracellular free calcium concentration. These effects were produced by the isolated B (binding) subunit of pertussis toxin, alone. Inositol phosphates production resulting from perturbation of the T cell antigen receptor-CD3 complex by MAb was not affected by pertussis toxin treatment but was markedly inhibited by cholera toxin. This effect of cholera toxin paralleled elevations in cAMP content. However, forskolin, in concentrations equipotent for cAMP production, was a weaker inhibitor of inositol phosphates production. Cholera toxin inhibition of inositol phosphates production did not result from inhibition of baseline incorporation of inositol into phosphoinositide substrates of phospholipase C. These studies underline the complexity of toxin effects on cellular systems and suggest that other approaches will be required to implicate guanine nucleotide-binding regulatory proteins in control of the early events of T lymphocyte activation. However, the data presented here provide a molecular basis for the clinical observations of lymphocytosis and the in vitro observations of lymphocyte mitogenesis after pertussis toxin stimulation.
Stewart
S J
SJ
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Prpic
V
V
Johns
J A
JA
Powers
F S
FS
Graber
S E
SE
Forbes
J T
JT
Exton
J H
JH
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D001427:Bacterial Toxins / Q000494:pharmacology*; D002460:Cell Line; D002772:Cholera Toxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D037342:Pertussis Toxin; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D001427:Bacterial Toxins; D007295:Inositol Phosphates; D011948:Receptors, Antigen, T-Cell; D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D002772:Cholera Toxin; D000242:Cyclic AMP; D037342:Pertussis Toxin