title: T cell exhaustion and Interleukin 2 downregulation.
abstract: T cells reactive to tumor antigens and viral antigens lose their reactivity when exposed to the antigen-rich environment of a larger tumor bed or viral load. Such non-responsive T cells are termed exhausted. T cell exhaustion affects both CD8+ and CD4+ T cells. T cell exhaustion is attributed to the functional impairment of T cells to produce cytokines, of which the most important may be Interleukin 2 (IL2). IL2 performs functions critical for the elimination of cancer cells and virus infected cells. In one such function, IL2 promotes CD8+ T cell and natural killer (NK) cell cytolytic activities. Other functions include regulating naïve T cell differentiation into Th1 and Th2 subsets upon exposure to antigens. Thus, the signaling pathways contributing to T cell exhaustion could be linked to the signaling pathways contributing to IL2 loss. This review will discuss the process of T cell exhaustion and the signaling pathways that could be contributing to T cell exhaustion.
authors.affiliation: Department of Medicine, Tufts Medical Center and Tufts University School of Medicine, Boston, MA, United States. Electronic address: Mumtaz.Yaseen@tufts.edu.
authors.forename: Mumtaz Y
authors.initials: MY
authors.lastname: Balkhi
authors.affiliation: Department of Medicine, Tufts Medical Center and Tufts University School of Medicine, Boston, MA, United States.
authors.forename: Qiangzhong
authors.initials: Q
authors.lastname: Ma
authors.affiliation: Boston University Medical Center, Boston, MA, United States.
authors.forename: Shazia
authors.initials: S
authors.lastname: Ahmad
authors.affiliation: Department of Medicine, Tufts Medical Center and Tufts University School of Medicine, Boston, MA, United States.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Junghans
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis; D001424:Bacterial Infections / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D002454:Cell Differentiation; D002843:Chromatin / Q000378:metabolism; D019295:Computational Biology; D015536:Down-Regulation; D044127:Epigenesis, Genetic; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000166:cytology; D010272:Parasitic Diseases / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D020413:3' Untranslated Regions; D002843:Chromatin; D007376:Interleukin-2; D012333:RNA, Messenger
keywords: Chromatin; Exhaustion; Interleukin 2; PD1; T cells