EFFECTS OF NICOTINE ON THE IMMUNE-RESPONSE .2. CHRONIC NICOTINE TREATMENT INDUCES T-CELL ANERGY

Previously, we have shown that both T and B lymphocytes from chronical ly nicotine-treated (NT) animals exhibit tolerance to activation by Ag s (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 tha t NT T cells significantly lose their ability to up-regulate inositol trisphosphate synthesis in response to TCR ligation or nonspecific act ivation of G proteins by AlF4-. However, increases in cAMP concentrati ons of T cells following activation of G protein-sensitive adenylate c yclase by cholera or pertussis toxin were not significantly affected b y the nicotine treatment, Interestingly, compared with control T cells , the background levels of inositol trisphosphate were significantly e levated in NT T cells, indicating some degree of activation in these c ells, This inference was further supported by observations that naive T cells from NT animals exhibit tyrosine phosphorylation of several su bstrates, including phospholipase C-yl, which were either absent or un derphosphorylated in unstimulated control T cells, Moreover, when, aft er 4-wk nicotine treatment, nicotine pumps were removed and serum coti nine levels fell to background, inhibition of the Ab-forming cells and Ca2+ responses continued for at least 2 more wk, These results sugges t that chronic in vivo nicotine exposure leads to T cell anergy and ma y contribute to nicotine/cigarette smoke-induced immunosuppression.