PD-1 has classically been used as a marker of T cell exhaustion in viral infection and in cancer [27]–[30], while other studies have found that cells expressing Tim-3 are dysfunctional and lack regulation [31], [32], and that coexpression of PD-1 and Tim-3 leads to extensive dysfunction of CD8+ T cells [33]. This evidence concerns the gene PDCD1 and viral infectious disease.