The Role Of Extrafollicular Helper T-like Cells In Patient With Chronic Graft-Versus-host Disease

Chronic graft-versus-host disease(cGVHD)is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Previous studies have shown that extrafollicular T follicular helper cells contribute to cGVHD in mice model,but the function of extrafollicular helper T cells during cGVHD pathogenesis in human remains largely unknown.In the current study,we identified circulating extrafollicular helper T-like cells(CD44hiCD62LloPSGL-1loCD4+,c-extrafollicular Th-like)in human peripheral blood.We performed phenotypic and functional analyses of c-extrafollicular Th-like cells from 80 patients after allo-HSCT to explore the role of these cells in the development of human cGVHD.Patients with active cGVHD had signifificantly higher frequencies and counts of c-extrafollicular Th-like cells than those of patients without cGVHD.The expansion of c-extrafollicular Th-like cells was more signifificant in patients with moderate/severe cGVHD than that of patients with mild cGVHD.C-extrafollicular Th-like cells from patients with active cGVHD exhibited increased functional abilities to induce plasmablast difffferentiation and IgG1 secretion compared to those of patients without cGVHD.Moreover,c-extrafollicular Th-like cell levels were highly correlated with the generation of autoreactive B cells,plasmablasts and IgGl antibodies.Our studies provide new insights into human cGVHD pathogenesis and identify c-extrafollicular Th-like cells as a key element in the development of human cGVHD.