Peripheral blood T helper cells circulate with pathogenic tissue resident T helper cells in chronic GVHD

Chronic graft versus host disease (cGVHD) is a systemic autoimmune-like syndrome. The role of Tph cells in the pathogenesis of cGVHD has not been examined, although previous studies have shown that cGVHD is characterized by loss of Tfh cells. Here, we show that in cGVHD patients and in a murine model that reflects characteristic features of human cGVHD, the proportions of Tph cells among CD4+ T cells in the blood were expanded. These cells augmented memory B cell differentiation and production of IgG via IL-21. Adoptive transfer experiments showed recirculation between Tph in the blood and tissue-resident T helper (Trh) cells in GVHD target tissues. The TCR repertoires of blood Tph cells and Trh cells in GVHD target tissues of mice were highly overlapping. Irradiated BALB/c recipient in receiving TCD-BM alone or plus 0.2M Thy1.2 cells from C57BL/6 H2Kb donor to establish No GVHD and cGVHD mouse model. PD1hiCXCR5- Tph cells from blood, CD69+ or CD69- PSGL1loPD1hi Trh cells from liver and lung of cGVHD recipients; Tfh cells from the spleen of No GVHD recipients were sorted out. mRNA from sorted cells were then isolated and processed for TCR repertiores sequencing.