title: Human CD4+ memory T cells are preferential targets for bystander activation and apoptosis.
abstract: There is much evidence that T cells may be activated via mechanisms that act independently of direct TCR ligation. Despite this, the question of whether such forms of bystander T cell activation occur during immune responses is hotly debated. To address some outstanding questions, we set up an in vitro system within which to analyze bystander T cell activation in human T cells, in the absence of the possibility for TCR cross-reactivity. In addition, we have investigated the genetic, phenotypic, and functional characteristics of bystander-activated T cells. In this study, we show that bystander T cell activation is, indeed, observed during a specific immune response, and that it occurs preferentially among CD4(+) memory T cells. Furthermore, bystander-activated T cells display a distinct gene expression profile. The mechanism for bystander T cell activation involves soluble factors, and the outcome is an elevated level of apoptosis. This may provide an explanation for the attrition of T cell memory pools of heterologous specificity during immune responses to pathogens such as viruses.
authors.affiliation: Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Bangs
authors.forename: Dilair
authors.initials: D
authors.lastname: Baban
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Cattan
authors.forename: Chris Ka-Fi
authors.initials: CK
authors.lastname: Li
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McMichael
authors.forename: Xiao-Ning
authors.initials: XN
authors.lastname: Xu
mesh_terms: D017209:Apoptosis / Q000276:immunology*; D024201:Bystander Effect / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction