CD8+ TILs, moreover, express upregulated immune-checkpoint co-inhibitory molecules such as programmed death-1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), T-cell immunoglobulin and mucin domain-3 (TIM-3), and lymphocyte activating 3 (LAG-3) (Figure 1), and the transcriptional profiling of these populations is reminiscent of that of hyporesponsive T cells classically exhausted by viral infections [155,156]. Here, CTLA4 is linked to viral infectious disease.