In summary, with murine models of chronic GVHD, we have found that extrafollicular CD4+ T and B interactions and CD4+ Trm cells in the GVHD target tissues play critical roles in chronic GVHD pathogenesis, and these findings have been linked to chronic GVHD pathogenesis in humans through studies with humanized MHC−/−HLA-A2+DR4+ NSG mice and patient GVHD target tissues (47). This evidence concerns the gene HLA-C and graft versus host disease.