Usage Information
Abstract
Chronic graft-versus-host disease (cGVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic transplantation. cGVHD pathophysiology involves cooperation between T follicular helper cells (TFHs) and germinal center B cells (GCBs), allo- and autoantibody depositions in cGVHD tissues, and fibrosis. We evaluated human CD19–directed chimeric antigen receptor (CAR19) T cell therapy in a clinically relevant murine cGVHD model with bronchiolitis obliterans syndrome (BOS). Although CD8+ CAR19 T cells effectively reduced peripheral B cell and GCB frequencies, pulmonary function was unimproved. In contrast, a single infusion of CAR19 CD4+ regulatory T cells (Tregs) mitigated ongoing pulmonary disease and modulated germinal centers (GCs) associated with reduced TFH frequencies compared with control Tregs but without measurable B cell depletion. Compared with EGFR Treg infusion, mice receiving CAR19 Tregs exhibited enhanced suppression of B cell activation and preserved splenic architecture, and CAR19 Treg infusion provided greater opportunities for interaction with CD19+ B cells at the B cell follicle boundary zones. Taken together with the absence of detectable B cell cytolysis, these findings were most consistent with GC suppression rather than B cell depletion as the dominant mechanism. Overall, our findings suggest that CAR19 Tregs represent a promising and safe cGVHD/BOS therapeutic strategy, offering immunosuppressive benefits and improved disease outcomes that may be more limited with CD8+ CAR19 T cell treatment.
Authors
Sujeong Jin, Michael C. Zaiken, Cameron McDonald-Hyman, Christina R. Hartigan, Sara Bolivar-Wagers, Jemma H. Larson, Yiyun Peng, Sophia Hani, Megan Riddle, Asim Saha, Angela Panoskaltsis-Mortari, Eun Ko, Yujie Zhao, Rocio Amaro Marquez, Pooja Shree Marri Baskar, Cindy R. Eide, William J. Murphy, Keli L. Hippen, Geoffrey R. Hill, Jakub Tolar, Peter T. Sage, Christopher A. Pennell, Leslie S. Kean, Bruce R. Blazar
Usage data is cumulative from July 2026 through August 2026.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 1,088 | 0 |
| 362 | 0 | |
| Figure | 10 | 0 |
| Supplemental data | 105 | 0 |
| Citation downloads | 224 | 0 |
| Totals | 1,789 | 0 |
| Total Views | 1,789 | |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.
