%0 Journal Article
%T IRF4 impedes human CD8 T cell function and promotes cell proliferation and PD-1 expression.
%A Hirsch T
%A Neyens D
%A Duhamel C
%A Bayard A
%A Vanhaver C
%A Luyckx M
%A Sala de Oyanguren F
%A Wildmann C
%A Dauguet N
%A Squifflet JL
%A Montiel V
%A Deschamps M
%A van der Bruggen P
%J Cell Rep
%V 43
%N 7
%D 2024 Jul 23
%M 38943641
暂无%R 10.1016/j.celrep.2024.114401
%X Human CD8 tumor-infiltrating lymphocytes (TILs) with impaired effector functions and PD-1 expression are categorized as exhausted. However, the exhaustion-like features reported in TILs might stem from their activation rather than the consequence of T cell exhaustion itself. Using CRISPR-Cas9 and lentiviral overexpression in CD8 T cells from non-cancerous donors, we show that the T cell receptor (TCR)-induced transcription factor interferon regulatory factor 4 (IRF4) promotes cell proliferation and PD-1 expression and hampers effector functions and expression of nuclear factor κB (NF-κB)-regulated genes. While CD8 TILs with impaired interferon γ (IFNγ) production exhibit activation markers IRF4 and CD137 and exhaustion markers thymocyte selection associated high mobility group box (TOX) and PD-1, activated T cells in patients with COVID-19 do not demonstrate elevated levels of TOX and PD-1. These results confirm that IRF4+ TILs are exhausted rather than solely activated. Our study indicates, however, that PD-1 expression, low IFNγ production, and active cycling in TILs are all influenced by IRF4 upregulation after T cell activation.