Differential regulation of human T cell and NK cell function by tobacco product preparations (P4339)

Abstract

Abstract NK cells and T cells play essential roles in innate and adaptive immune responses by protecting against microbial infections and in tumor surveillance. While smoking is known to cause immunosuppression, it is unclear how the use of smokeless tobacco (ST) products affects immune responses. We investigated immunological responses to exposure of reference tobacco product preparations (TPPs) using poly I:C and LPS-stimulated PBMCs. The TPPs included whole smoke-conditioned media (WS-CM) and total particulate matter (TPM) prepared from 3R4F reference cigarettes, 2S3 moist snuff smokeless tobacco extracted in complete artificial saliva (ST/CAS), and nicotine. WS-CM and TPM treatment resulted in dose-dependent reductions in the expression of intracellular IFN-γand TNF-α in NK cells and T cells, secretion of several cytokines by PBMCs and the inhibition of cytolytic activity of effector cells in PBMCs. Although interference from the vehicle effects confounded the interpretation of data from cells exposed to ST/CAS, some immunosuppressive effects were evident only at high doses. Treatment with nicotine caused minimal immunosuppression in this system. These data suggest that the function of human NK cells and T cells is impacted by exposure to TPPs, on an equi-nicotine unit basis, as follows: WS-CM > TPM >ST/CAS> nicotine. These findings support the hypothesis that immune-suppression from smoking is linked to a higher incidence of microbial infections and cancer among smokers.