title: Differential sensitivity of naïve and memory subsets of human CD8+ T cells to TNF-alpha-induced apoptosis.
abstract: In this investigation, we have examined the relative sensitivity of human naïve, central memory (T(CM)), and two types of effector memory CD8+ T cells (T(EM) and T(EMRA)) to TNF-alpha-induced apoptosis. Our data show that naïve and T(CM) CD8+ T cells were sensitive, whereas T(EM) and T(EMRA) CD8+ T cells were relatively resistant to TNF-alpha-induced apoptosis. The apoptosis profile correlated with the activation of caspase-8 and caspase-3. However, no correlation was observed between relative sensitivity of four CD8+ T cell subsets to apoptosis and the expression of TNFR-I or TNFR-II. T(EM) and T(EMRA) CD8+ T cells displayed increased phosphorylation of IKKalpha/beta and IkappaB and increased NF-kappaB activity as compared to naïve and T(CM) CD8+ T cells. Bcl-2, Bcl-x(L) and FLIP(L) expression was higher and Bax expression was lower in T(EM) and T(EMRA) CD8+ T cells as compared to naïve and T(CM) CD8+ T cells. These data suggest that signaling molecules downstream of TNFRs may be responsible for differential sensitivity among subsets of CD8+ T cells to TNF-alpha-induced apoptosis.
authors.affiliation: Division of Basic and Clinical Immunology, University of California, Irvine, California 92697, USA. sgupta@uci.edu
authors.forename: Sudhir
authors.initials: S
authors.lastname: Gupta
authors.forename: Houfen
authors.initials: H
authors.lastname: Su
authors.forename: Ruifen
authors.initials: R
authors.lastname: Bi
authors.forename: Sastry
authors.initials: S
authors.lastname: Gollapudi
mesh_terms: D000328:Adult; D017209:Apoptosis; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D020672:I-kappa B Proteins; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D051020:bcl-X Protein; D051550:I-kappa B Kinase; D053148:Caspase 3; D053181:Caspase 8