A role for the transcriptional repressor Blimp-1 in CD8(+) T cell exhaustion during chronic viral infection.
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.
Shin
Haina
H
Immunology Program and Wistar Vaccine Center, The Wistar Institute, Philadelphia, PA 19104, USA.
Blackburn
Shawn D
SD
Intlekofer
Andrew M
AM
Kao
Charlly
C
Angelosanto
Jill M
JM
Reiner
Steven L
SL
Wherry
E John
EJ
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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