03.29.21

Targeting tissue-resident T cells a potential treatment pathway for cGVHD

The following content was featured in a recent Abstracts newsletter distributed by ASTCT. The Abstracts newsletter highlights the latest research in the clinical research and translational science studies aspects of transplantation and cellular therapy. 

Kong X, Zeng D, Wu X, et al. Tissue-Resident PSGL1lo CD4+ T Cells Promote B Cell Differentiation and Chronic Graft-Versus-Host Disease-Associated Autoimmunity. Journal of Clinical Investigation. 2021; 131 (1) (doi: 10.1172/JCI135468).

A potential new pathway for prophylaxis and treatment of chronic graft-versus-host disease (cGVHD) and other autoimmune disorders involves targeting tissue-resident T cells. Scientists already know that interactions between CD4+ T cells and B cells contribute to the pathogenesis of cGVHD, but new evidence delves further. The study, led by the Becker Research Institute of City of Hope, employed murine and humanized MHC–/–HLA-A2+DR4+ murine models of cGVHD. The data suggest that peripheral PSGL1hiCD4+ T cells interact with host cells in lymphoid tissue, differentiating into PSGL1lo CD4+ T cells that mimic B cell helpers. Subsequently, the PSGL1loCD4+ T cells from GVHD target tissues then become tissue-resident memory T cells. The interaction between these and memory B cells triggers memory B cell differentiation into autoreactive plasma cells, which produce IgG antibodies that augment GVHD tissue damage. The potential of tissue-resident T cells to treat antibody-mediated features of autoimmune disease deserves further attention, the investigators conclude.

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