Tissue-resident PSGL1loCD4+ T cells promote B cell differentiation and chronic graft-versus-host disease–associated autoimmunity
- 4 January 2021
- journal article
- research article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 131 (1)
- https://doi.org/10.1172/jci135468
Abstract
CD4+ T cells interactions with B cells play a critical role in the pathogenesis of systemic autoimmune diseases such as systemic lupus and chronic graft-versus-host disease (cGVHD). Extrafollicular CD44hiCD62LloPSGL1loCD4+ (PSGL1loCD4+) T cells are associated with the pathogenesis of lupus and cGVHD, but their causal role has not been established. With murine and humanized MHC–/–HLA-A2+DR4+ murine models of cGVHD, we show that both murine and human PSGL1loCD4+ T cells from GVHD target tissues have features of B cell helpers with upregulated-expression of PD1 and ICOS and production of IL-21. They reside in non-lymphoid tissues without circulating in the blood and have features of tissue-resident memory T cells with upregulated-expression of CD69. Murine PSGL1loCD4+ T cells from GVHD target tissues augmented B cell differentiation into plasma cells and production of autoantibodies via their PD1 interaction with PD-L2 on B cells. Human PSGL1loCD4+ T cells were apposed with memory B cells in the liver tissues of humanized mice and cGVHD patients. Human PSGL1loCD4+ T cells from humanized GVHD target tissues also augmented autologous memory B cell differentiation into plasma cells and antibody production in PD1/PD-L2-dependent manner. Further preclinical studies targeting tissue-resident T cells to treat antibody-mediated features of autoimmune diseases are warranted.Funding Information
- National Institutes of Health (R01 AI066008,R01 CA228465)
- NCI (P30CA033572.)
This publication has 50 references indexed in Scilit:
- Spatial and functional heterogeneity of follicular helper T cells in autoimmunityCurrent Opinion in Immunology, 2019
- T Follicular Helper Cell Biology: A Decade of Discovery and DiseasesImmunity, 2019
- Antibodies from donor B cells perpetuate cutaneous chronic graft-versus-host disease in miceBlood, 2016
- Donor B Cells in Transplants Augment Clonal Expansion and Survival of Pathogenic CD4+ T Cells That Mediate Autoimmune-like Chronic Graft-versus-Host DiseaseThe Journal of Immunology, 2012
- PD-1 regulates germinal center B cell survival and the formation and affinity of long-lived plasma cellsNature Immunology, 2010
- Graft-versus-host diseaseThe Lancet, 2009
- ICOS-dependent extrafollicular helper T cells elicit IgG production via IL-21 in systemic autoimmunityThe Journal of Experimental Medicine, 2008
- Donor CD4+ T and B cells in transplants induce chronic graft-versus-host disease with autoimmune manifestationsBlood, 2006
- Engagement of the Pd-1 Immunoinhibitory Receptor by a Novel B7 Family Member Leads to Negative Regulation of Lymphocyte ActivationThe Journal of Experimental Medicine, 2000
- Insights into the Molecular Basis of Leukocyte Tethering and Rolling Revealed by Structures of P- and E-Selectin Bound to SLeX and PSGL-1Cell, 2000