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A role for the transcriptional repressor
Blimp-1 in CD8(+) T cell exhaustion during chronic viral
infection
Shin H, Blackburn SD, Intlekofer AM, Kao C, Angelosanto
JM, Reiner SL, Wherry EJ Immunity. 2009 31:178-80.
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.
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