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"Since cytotoxic CD4+ T cells preferentially eliminated MHC II-ex- pressing CD19+ cells, why was the frequency of cytotoxic CD4+ T cells positively correlated with the frequency of MHC II-expressing CD19+ cells? One possibility is that the development of tumor-reactive cyto- toxic CD4+ T cells requires an abundance of MHC II-expressing tumor cells. Also, since the study was performed in an in vitro condition, it is unlikely to capture all the complexities of an in vivo system. In the human body, the MHC II-expressing CD19+ cells may be quickly re- plenished via proliferation. In addition, it was found that IL-10-ex- pressing CD4+Foxp3- Tr1 cells could produce granzymes and perforin and therefore, in our experimental system, the cytolytic molecule-ex- pressing Tr1 cells could not be distinguished from other cytotoxic CD4+ T cells. "