Vol. 302, Issue 3, 935-939, September 2002

Chronic Self-Administration of Nicotine in Rats Impairs T Cell Responsiveness

Roma Kalra, Shashi P. Singh, Dean Kracko, Shannon G. Matta, Burt M. Sharp and Mohan L. Sopori

Immunology Program, Lovelace Respiratory Research Institute, Albuquerque, New Mexico (R.K., S.P.S., D.K., M.L.S.); and Department of Pharmacology, University of Tennessee Health Science Center, Memphis, Tennessee (S.G.M., B.M.S.)

Chronic exposure of rodents to nicotine via subcutaneously or intracerebroventricularly implanted miniosmotic pumps affects T cell function. However, this method of continuous nicotine administration does not replicate the self-motivated administration of nicotine in human smokers. To determine whether nicotine impairs the immune system under conditions pertinent to human smokers, we investigated the T cell responsiveness of male Lewis rats self-administering (SA) nicotine (0.03 mg/kg of body weight per injection) 40 to 50 times/day for 5 weeks, using a model of virtually unlimited access to nicotine. Compared with sham control animals, the concanavalin A-induced proliferation of spleen cells from SA rats was significantly decreased. Moreover, the ability of spleen cells to mobilize intracellular Ca²⁺ after ligation of the T cell antigen receptor (TCR) with an anti- TCR antibody was significantly less in SA than in control rats. In addition, inositol 1,4,5-trisphosphate (IP₃)-sensitive intracellular Ca²⁺ stores were markedly depleted in spleen cells from SA animals. These results suggest that chronic nicotine self-administration suppresses T cell responsiveness, and this suppression may result from an impaired TCR-mediated signaling that stems from the depletion of IP₃-sensitive intracellular Ca²⁺ stores.