The effect of nicotine on murine CD4 T cell responses.
T cells were exposed to various concentrations of nicotine or smokeless tobacco extract (STE) during in vitro immune responses in order to examine effects upon expression of T cell costimulatory counter-receptors, CD28 and CTLA-4, and cytokine production. Splenic mononuclear cells (SPM) were exposed to 1:10(2) to 1:10(3) dilutions of STE or 1-100 micrograms/ml nicotine during 48 and 72 h of stimulation with anti-CD3. Expression of CD28 and CTLA-4 was evaluated with flow cytometry and production and expression of IL-2, IL-4, IL-10 and IFN-gamma were evaluated using ELISA and RT-PCR. The data here indicate that the percentage of CD4+ T cells expressing CD28 declined while percentage and intensity of CTLA-4 expression increased with exposure to a 1:10(2) dilution of STE during the T cell response. Exposure to nicotine decreased the percentage of CD4+ T cells expressing both CD28 and CTLA-4 and decreased the intensity of CD28 expression. Responding T cells exposed to nicotine produced significantly less Th1 cytokines, IL-2 and IFN-gamma, but significantly more Th2 cytokines, IL-4 and IL-10. Cytokine specific mRNA expression was only slightly affected by the exposure to nicotine. Thus, exposure of T cells to physiological concentrations of STE or nicotine can alter the T cell expression of CD28 and CTLA-4, and the CD4 T cell cytokine expression pattern.
Zhang
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Department of Oral Biology, College of Dentistry, University of Nebraska Medical Center, Lincoln 68583, USA.
Petro
T M
TM
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000096:biosynthesis; D018106:CD28 Antigens / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D060908:CTLA-4 Antigen; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects; D005260:Female; D018796:Immunoconjugates; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D009538:Nicotine / Q000494:pharmacology*; D010947:Plants, Toxic; D013154:Spleen / Q000166:cytology; D014030:Tobacco, Smokeless / Q000633:toxicity
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D016207:Cytokines; D018796:Immunoconjugates; D009538:Nicotine; D000069594:Abatacept