Furthermore, Riches et al. noted chronic lymphocytic leukemia specific CD8+ T cells exhibited increased PD-1 expression and an exhausted phenotype, despite no functional difference in cytokine production [32], while Amarnath et al. showed conversion of CD4+ T cells to T regulatory cells following stimulation of the PD-1 receptor by its ligand PD-L1 [33]. This evidence concerns the gene CD4 and B-cell chronic lymphocytic leukemia.