Figure 1.

Induction of WT1-specific CD4⁺ and CD8⁺ T cell responses by dendritic cells pulsed with MHC class I/II restricted multiple WT1 peptides. To activate WT1-specific CD4⁺ helper and CD8⁺ cytotoxic T cells simultaneously, dendritic cells (DCs) are pulsed with three types of WT1 peptide mixtures restricted by MHC class I/II (DC/WT1-I/II). After injection of DC/WT1-I/II, DC/WT1-I/II migrate to regional lymph nodes, reside in the T cell area, closely interact with T cells, and activate WT1-specific CD4⁺ and CD8⁺ T cells. WT1-specific CD4⁺ T cells provide help to the WT1-specific CD8⁺ T cells by secreting several cytokines. Programmed death-ligand 1 (PD-L1) on tumor cells is induced by IFNγ, which is predominantly produced by CD4⁺ helper type 1 cells. The overexpression of PD-L1 on tumor cells and the lower frequency of WT1-specific programmed cell death protein 1 (PD-1)⁺ CD8⁺ T cells may be associated with long-term survival.