title: 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) regulates CTL activation and memory programming.
abstract: 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is one of the major carcinogens in tobacco. NNK has been associated with various cancers in tobacco users, especially lung cancer. However, the effects of NNK on cytotoxic T lymphocytes (CTLs), the cells responsible for destrcution of maligant and pathogen-infected cells, has not been elucidated. Using transgenic CTLs in vitro and in vivo, we show that NNK can directly affect CTL activation. NNK can enhance the expression of adhesion molecule CD62L in CTLs during their activation in vitro, but has no effects on their expansion and production of effector molecules such as IFN and granzyme B. After transferred into recipient mice, however, the NNK pretreated CTLs suffer an early loss in expansion. The percentage of memory precursors is higher in NNK pretreated CTLs, but the total amount of memory precursors is similar to controls. The final memory CTL population from NNK pretreated CTLs is reduced, but sustains a more central memory phenotype. In conclusion, NNK can affect CTL activation by modulating adhension molecule expression and reducing memory programming.
authors.affiliation: Department of Animal and Avian Sciences, University of Maryland, College Park, MD 20742, USA.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Sun
authors.forename: Zhengguo
authors.initials: Z
authors.lastname: Xiao
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D007156:Immunologic Memory / Q000187:drug effects*; D019041:L-Selectin / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009602:Nitrosamines / Q000633:toxicity*; D012907:Smoking / Q000009:adverse effects / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology*
chemical_list: D002273:Carcinogens; D009602:Nitrosamines; D019041:L-Selectin; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone