Delayed IL-21 treatment preferentially expands peptide-specific CD8 + T cells by reducing bystander activation of T cells

We previously reported a simple and practical procedure to generate peptide-specific CD8 T cells using peptide and IL-2, which is applied to produce human telomerase reverse transcriptase (hTERT)-specific CD8+ T cells for clinical use. We have modified the procedure to enhance the amplification of peptide-specific CD8 T cells adding IL-21. Using human leukocyte antigen (HLA)-A*0201-restricted cytomegalovirus/pp65-specific CD8 T cells of healthy volunteers, we optimized the culture conditions by adjusting the dose and timing of IL-21 treatment. By adding IL-21, we accelerated the expansion rate of cytomegalovirus/pp65-specific CD8 T cells by reducing bystander activation of T cells. We expect that the procedure including IL-21 would improve the production rate of hTERT- and Wilms tumor 1 (WT1)-specific CD8 T cells for clinical trials.