These results suggest that CD276-expressing memory CD4+ T cells represent GVHD-triggering TH1 cells and their selective depletion from the donor graft can provide better control of GVHD in HLA-mismatched HSCT such as in haplo settings but not in HLA-matched HSCT such as transplant from matched unrelated donor where many if not most minor antigens are mismatched. Here, CD4 is linked to graft versus host disease.