title: High-Dose Nicotinamide Suppresses ROS Generation and Augments Population Expansion during CD8(+) T Cell Activation.
abstract: During T cell activation, mitochondrial content increases to meet the high energy demand of rapid cell proliferation. With this increase, the level of reactive oxygen species (ROS) also increases and causes the rapid apoptotic death of activated cells, thereby facilitating T cell homeostasis. Nicotinamide (NAM) has previously been shown to enhance mitochondria quality and extend the replicative life span of human fibroblasts. In this study, we examined the effect of NAM on CD8(+) T cell activation. NAM treatment attenuated the increase of mitochondrial content and ROS in T cells activated by CD3/CD28 antibodies. This was accompanied by an accelerated and higher-level clonal expansion resulting from attenuated apoptotic death but not increased division of the activated cells. Attenuation of ROS-triggered pro-apoptotic events and upregulation of Bcl-2 expression appeared to be involved. Although cells activated in the presence of NAM exhibited compromised cytokine gene expression, our results suggest a means to augment the size of T cell expansion during activation without consuming their limited replicative potential.
authors.affiliation: Department of Life Science, University of Seoul, Seoul 130-743, Korea.
authors.forename: Ho Jin
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: Department of Life Science, University of Seoul, Seoul 130-743, Korea.
authors.forename: So-Young
authors.initials: SY
authors.lastname: Jang
authors.affiliation: Department of Life Science, University of Seoul, Seoul 130-743, Korea.
authors.forename: Eun Seong
authors.initials: ES
authors.lastname: Hwang
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009536:Niacinamide / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: C000595707:BCL2 protein, human; D016207:Cytokines; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D009536:Niacinamide
keywords: ROS; T cell activation; mitochondria; nicotinamide