Effects of nicotine exposure on T cell development in fetal thymus organ culture: arrest of T cell maturation.
There is evidence for both physiological functions of the natural neurotransmitter, acetylcholine, and pharmacological actions of the plant alkaloid, nicotine, on the development and function of the immune system. The effects of continuous exposure to nicotine over a 12-day course of fetal thymus organ culture (FTOC) were studied, and thymocytes were analyzed by flow cytometry. In the presence of very low concentrations of nicotine many more immature T cells (defined by low or negative TCR expression) and fewer mature T cells (intermediate or high expression of TCR) were produced. In addition, the numbers of cells expressing CD69 and, to a lesser extent, CD95 (Fas) were increased. These effects took place when fetal thymus lobes from younger (13-14 days gestation) pups were used for FTOC. If FTOC were set up using tissue from older (15-16 days gestation pups), nicotine had little effect, suggesting that it may act only on immature T cell precursors. Consistent with an increase in immature cells, the expression of recombinase-activating genes was found to be elevated. Nicotine effects were partially blocked by the simultaneous addition of the nicotinic antagonist d-tubocurarine. Furthermore, d-tubocurarine alone blocked the development of both immature and mature murine thymocytes, suggesting the presence of an endogenous ligand that may engage nicotinic acetylcholine receptors on developing thymocytes and influence the course of normal thymic ontogeny.
Middlebrook
Aaron J
AJ
Department of Microbiology and Immunology, University of Arizona College of Medicine, Tucson, AZ 85274, USA.
Martina
Cherie
C
Chang
Yung
Y
Lukas
Ronald J
RJ
DeLuca
Dominick
D
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002462:Cell Membrane / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D005333:Fetus / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D016654:Genes, RAG-1 / Q000187:drug effects; D006131:Growth Inhibitors / Q000494:pharmacology*; D037181:Lectins, C-Type; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D009538:Nicotine / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009924:Organ Culture Techniques; D011978:Receptors, Nicotinic / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D014403:Tubocurarine / Q000494:pharmacology; D019014:fas Receptor / Q000096:biosynthesis; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; D037181:Lectins, C-Type; D009538:Nicotine; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D014403:Tubocurarine; D019014:fas Receptor; D000099192:CD69 Antigens; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2