Background: Lymphocyte homing to secondary lymphoid organs is thought to be required for initiation of the alloreactive immune response. Because CCR7 is the essential chemokine receptor responsible for lymphocyte and dendritic cell homing to secondary lymphoid organs, allograft survival was analyzed in CCR7-deficient (CCR7) mice.
Methods: Heterotopic heart and skin allotransplantation was performed in CCR7 and wild-type (WT) recipients. Graft survival was monitored daily. Grafts and draining lymph nodes were analyzed by immunohistology and flow cytometry at different time points. Groups of mice were splenectomized at the day of allotransplantation.
Results: A significant though modest prolongation of allograft survival in CCR7 recipients was observed for heart grafts (WT, 7.3 +/- 0.5 days; CCR7, 10.7 +/- 2.8 days) and skin grafts (WT, 8.9 +/- 0.9 days; CCR7, 12.3 +/- 0.9 days). This was accompanied by a delay in the cellular infiltration of allografts. T-cell accumulation and expansion in the draining lymph nodes in CCR7 recipients was severely impaired. Splenectomy had only a moderate prolongation effect on allograft survival in CCR7 mice.
Conclusions: These results suggest that CCR7-dependent processes support allograft rejection yet are dispensable for the rejection response.
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http://dx.doi.org/10.1097/01.tp.0000131159.25845.eb | DOI Listing |
Sci Transl Med
January 2025
Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA.
Long-term, immunosuppression-free allograft survival has been induced in human and nonhuman primate (NHP) kidney recipients after nonmyeloablative conditioning and donor bone marrow transplantation (DBMT), resulting in transient mixed hematopoietic chimerism. However, the same strategy has consistently failed in NHP heart transplant recipients. Here, we investigated whether long-term heart allograft survival could be achieved by cotransplanting kidneys from the same donor.
View Article and Find Full Text PDFAdv Wound Care (New Rochelle)
January 2025
Rubrum Advising, Fort Washington, Pennsylvania, USA.
Lower-extremity diabetic ulcers (LEDUs) affect more than 500,000 U.S. Medicare beneficiaries each year.
View Article and Find Full Text PDFFront Immunol
January 2025
Department of Hematology and Transplantology, Medical University of Gdansk, Gdansk, Poland.
Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare complement-driven acquired hemolytic anemia with specific presentations of hemoglobinuria, abdominal pain, fatigue, and thrombosis.
Objective: To review the current therapeutic strategies for PNH, including anti-complement therapy and allogeneic hematopoietic cell transplantation (alloHCT), focusing on the tailoring of the approach to the disease subtype.
Results: The outcome of alloHCT varies depending on disease severity, thrombotic history, and response to prior therapies.
Front Immunol
January 2025
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) constitutes a critical therapeutic approach for patients with malignant hematological disorders. Nevertheless, acute graft-versus-host disease (GVHD), one of the most prevalent complications associated with HSCT, remains a leading contributor to non-relapse mortality. In recent years, there has been an increasing focus on the interplay between chemokines and their receptors in the context of acute GVHD.
View Article and Find Full Text PDFFront Immunol
January 2025
Institut Català d'Oncologia - Hospital Duran i Reynals, IDIBELL, Universitat de Barcelona, Barcelona, Spain.
Introduction: This multicenter prospective study sponsored by the (GETH-TC) explores the use of frailty assessments in allo-HCT candidates.
Methods: Frailty was measured using the HCT Frailty Scale at first consultation and HCT admission in 404 adults from 15 HCT programs in Spain. Based on the results, patients were classified into fit, pre-frail and frail categories.
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