CD4 and neoplasm: Our study further indicated that A20-silenced Mф-induced cytotoxic CD4+ T cell differentiation is MHC class-II restricted, which coincides with published studies that tumor-reactive CD4+ T cells develop cytotoxic activity in an MHC class-II-dependent manner [34] and priming of tumor-reactive CD4+ T cells requires MHC class-II expression on recipient or host cells, not on tumor cells [1], [2], [27].