title: A role for the transcriptional repressor Blimp-1 in CD8(+) T cell exhaustion during chronic viral infection.
abstract: T cell exhaustion is common during chronic infections and can prevent optimal immunity. Although recent studies have demonstrated the importance of inhibitory receptors and other pathways in T cell exhaustion, the underlying transcriptional mechanisms are unknown. Here, we define a role for the transcription factor Blimp-1 in CD8(+) T cell exhaustion during chronic viral infection. Blimp-1 repressed key aspects of normal memory CD8(+) T cell differentiation and promoted high expression of inhibitory receptors during chronic infection. These cardinal features of CD8(+) T cell exhaustion were corrected by conditionally deleting Blimp-1. Although high expression of Blimp-1 fostered aspects of CD8(+) T cell exhaustion, haploinsufficiency indicated that moderate Blimp-1 expression sustained some effector function during chronic viral infection. Thus, we identify Blimp-1 as a transcriptional regulator of CD8(+) T cell exhaustion during chronic viral infection and propose that Blimp-1 acts as a transcriptional rheostat balancing effector function and T cell exhaustion.
authors: Immunology Program and Wistar Vaccine Center, The Wistar Institute, Philadelphia, PA 19104, USA.
authors: Haina
authors: H
authors: Shin
authors: Shawn D
authors: SD
authors: Blackburn
authors: Andrew M
authors: AM
authors: Intlekofer
authors: Charlly
authors: C
authors: Kao
authors: Jill M
authors: JM
authors: Angelosanto
authors: Steven L
authors: SL
authors: Reiner
authors: E John
authors: EJ
authors: Wherry
mesh_terms: D000208:Acute Disease; D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D002454:Cell Differentiation / Q000276:immunology; D002908:Chronic Disease; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D058851:GPI-Linked Proteins; D053804:Granzymes / Q000276:immunology / Q000378:metabolism; D007156:Immunologic Memory / Q000276:immunology*; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D000074462:Positive Regulatory Domain I-Binding Factor 1; D061026:Programmed Cell Death 1 Receptor; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism; D000071176:Signaling Lymphocytic Activation Molecule Family; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014777:Virus Diseases / Q000235:genetics / Q000276:immunology*; D000093322:Lymphocyte Activation Gene 3 Protein
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; C511585:Cd160 protein, mouse; C490007:Cd244a protein, mouse; D058851:GPI-Linked Proteins; C491383:Pdcd1 protein, mouse; C513258:Prdm1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family; D014157:Transcription Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1; D053804:Granzymes; D000093322:Lymphocyte Activation Gene 3 Protein