Expansion of circulating extrafollicular helper T-like cells in patients with chronic graft-versus-host disease. (June 2019)

• Record Type: Journal Article
• Authors: Jin, Hua; Yang, Kaibo; Zhang, Haiyan; Chen, Yanqiu; Qi, Hanzhou; Fan, Zhiping; Huang, Fen; Xuan, Li; Lin, Ren; Zhao, Ke; Liu, Qifa
• Is Part Of: Journal of autoimmunity. Volume 100(2019)
• Page Start: 95
• Page End: 104
• Publication Date: 2019-06
• Subjects: Circulating extrafollicular helper T-like cells -- T follicular helper cells -- Chronic graft-versus-host disease -- Allogeneic hematopoietic stem cell transplantation; Autoimmunity -- Periodicals; Autoimmune diseases -- Periodicals; Autoantibodies -- Periodicals; Autoimmune Diseases -- Periodicals; Auto-immunité -- Périodiques; Maladies auto-immunes -- Périodiques; Electronic journals; 616.978005
• DOI: 10.1016/j.jaut.2019.03.006
• Languages: English
• ISSNs: 0896-8411

Abstract

Abstract: 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 T follicular helper cells (Tfh) contribute to immune pathology in cGVHD, but the function of extrafollicular helper T cells during cGVHD pathogenesis remains largely unknown. In the current study, we identified circulating extrafollicular helper T-like cells (CD44 hi CD62L lo PSGL-1 lo CD4 +, 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 significantly 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 significant 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 differentiation 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 IgG1 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. Highlights: Circulating extrafollicular helper T-like cells expand in patients with cGVHD. C-extrafollicular Th-like cells correlate with the generation of plasmablasts. C-extrafollicular Th-like cells correlate with the generation of IgG1 antibodies.