Effects of nicotine on the immune response. II. Chronic nicotine treatment induces T cell anergy.
Previously, we have shown that both T and B lymphocytes from chronically nicotine-treated (NT) animals exhibit tolerance to activation by Ags (ligation of Ag receptors), as indicated by their decreased ability to mobilize intracellular calcium and, at least in T cells, arrest of cells in the G0/G1 phase of the cell cycle. Herein, we demonstrate that NT T cells significantly lose their ability to up-regulate inositol trisphosphate synthesis in response to TCR ligation or nonspecific activation of G proteins by AIF-4. However, increases in cAMP concentrations of T cells following activation of G protein-sensitive adenylate cyclase by cholera or pertussis toxin were not significantly affected by the nicotine treatment. Interestingly, compared with control T cells, the background levels of inositol trisphosphate were significantly elevated in NT T cells, indicating some degree of activation in these cells. This inference was further supported by observations that naive T cells from NT animals exhibit tyrosine phosphorylation of several substrates, including phospholipase C-gamma1, which were either absent or underphosphorylated in unstimulated control T cells. Moreover, when, after 4-wk nicotine treatment, nicotine pumps were removed and serum cotinine levels fell to background, inhibition of the Ab-forming cells and Ca2+ responses continued for at least 2 more wk. These results suggest that chronic in vivo nicotine exposure leads to T cell anergy and may contribute to nicotine/cigarette smoke-induced immunosuppression.
Geng
Y
Y
Immunotoxicology Section, Insitute of Basic and Applied Medical Research, The Lovelace Insitutes, Albuquerque, NM 87108, USA.
Savage
S M
SM
Razani-Boroujerdi
S
S
Sopori
M L
ML
D017607:Aluminum Compounds / Q000494:pharmacology; D000818:Animals; D000917:Antibody Formation; D000941:Antigens / Q000008:administration & dosage; D002118:Calcium / Q000378:metabolism; D004912:Erythrocytes / Q000276:immunology; D005459:Fluorides / Q000494:pharmacology; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D051966:Phospholipase C gamma; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D012756:Sheep; D015398:Signal Transduction; D012907:Smoking / Q000009:adverse effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D017607:Aluminum Compounds; D000941:Antigens; D007527:Isoenzymes; D011948:Receptors, Antigen, T-Cell; D014443:Tyrosine; D009538:Nicotine; D015544:Inositol 1,4,5-Trisphosphate; D011505:Protein-Tyrosine Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D005459:Fluorides; D002118:Calcium; C032311:aluminum fluoride