Positive expression of iRs such as PD1, CTLA-4, TIM3, LAG-3, 2B4, CD160, and BTLA has been directly linked to reduced cytokine production by T cells from cancer patients (including reports from our group) or in the chronic LCMV mouse model of “T cell exhaustion” and other viral infections (7, 13, 19–23). This evidence concerns the gene CTLA4 and viral infectious disease.