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18, 19, 20, 21, 22 Recent efforts have proposed that specific transcription factors such as T-bet were associated with T-cell exhaustion, which were supported by the evidence that T-bet directly repressed transcription of the gene encoding PD-1, and high T-bet expression sustained exhausted CD8 + T cells in mice infected with LCMV, 23 reminiscent of its role in sustaining exhausted CD4 + T cells

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