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Outcomes in transplantation have been limited by suboptimal long-term graft survival and toxicities associated with current immunosuppressive approaches. T cell costimulation blockade has shown promise as an alternative strategy to avoid the side effects of conventional immunosuppressive therapies, but targeting CD28-mediated costimulation alone has proven insufficient to prevent graft rejection in primates. Donor-specific memory T (TM) cells have been implicated in costimulation blockade-resistant transplant rejection, due to their enhanced effector function and decreased reliance on costimulatory signaling. Thus, we have tested a potential strategy to overcome TM cell-driven rejection by targeting molecules preferentially expressed on these cells, such as the adhesion molecule lymphocyte function-associated antigen 1 (LFA-1). Here, we show that short-term treatment (i.e., induction therapy) with the LFA-1-specific antibody TS-1/22 in combination with either basiliximab (an IL-2Rα-specific mAb) and sirolimus (a mammalian target of rapamycin inhibitor) or belatacept (a high-affinity variant of the CD28 costimulation-blocker CTLA4Ig) prolonged islet allograft survival in nonhuman primates relative to control treatments. Moreover, TS-1/22 masked LFA-1 on TM cells in vivo and inhibited the generation of alloproliferative and cytokine-producing effector T cells that expressed high levels of LFA-1 in vitro. These results support the use of LFA-1-specific induction therapy to neutralize costimulation blockade-resistant populations of T cells and further evaluation of LFA-1-specific therapeutics for use in transplantation.
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http://dx.doi.org/10.1172/JCI43895 | DOI Listing |
J Int Med Res
December 2024
Department of Urology, Shaoxing People's Hospital, Shaoxing, Zhejiang, China.
renal transplant carcinoma, especially in the context of bilateral renal carcinoma, is rare and often presents as small, low-grade papillary renal cell carcinoma (RCC). There is currently no consensus or effective treatment for advanced metastatic RCC after kidney transplantation. A 40-year-old man developed renal transplant carcinoma with venous thrombus and lung metastases 13 years after transplantation.
View Article and Find Full Text PDFExpert Rev Respir Med
December 2024
Division of Thoracic Surgery, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Introduction: Situs inversus is a rare congenital condition where the organs in the chest and abdomen are reversed, thus complicating surgeries such as lung transplantation. Kartagener syndrome (KS), associated with situs inversus, includes chronic sinusitis and bronchiectasis, which can progress to end-stage lung disease requiring transplantation. This review discusses the unique surgical considerations, technical challenges, and outcomes of lung transplantation in patients with situs inversus, particularly KS.
View Article and Find Full Text PDFTransplantation
December 2024
Department of Transplant, Mayo Clinic Florida, Jacksonville, FL.
Background: The availability of in situ normothermic regional perfusion (NRP) or ex situ normothermic machine perfusion (NMP) has revolutionized donation after circulatory death (DCD) liver transplant (LT). While some have suggested that NRP and NMP may represent competing technologies for DCD LT, there are many scenarios where these technologies can function in a complementary manner.
Methods: Between January 2022 and March 2024, 83 DCD LTs were performed using NRP (62 NRP alone and 21 NRP + NMP) and were compared with 297 static cold storage (SCS) DCD LTs.
Kidney transplantation (KT) is the treatment of choice for chronic kidney disease (CKD) patients, but there is a continued loss of grafts in the long-term (50% at 10 years) due to either patient 's death or chronic allograft dysfunction. Metabolic syndrome (MS) is very prevalent after KT (30-40%) and its components contribute to the appearance of non-alcoholic fatty liver disease/metabolic dysfunction-associated fatty liver disease (NAFLD/MAFLD) and non-alcoholic steatohepatitis (NASH), which represents the hepatic component of MS. Furthermore, about 20-40% of KT recipients present early graft inflammation, including subclinical inflammation.
View Article and Find Full Text PDFLong-term allograft survival is limited by humoral-associated chronic allograft rejection, suggesting inadequate constraint of humoral alloimmunity by contemporary immunosuppression. Heterogeneity in alloreactive B cells and the incomplete definition of which B cells participate in chronic rejection in immunosuppressed transplant recipients limits our ability to develop effective therapies. Using a double-fluorochrome single-HLA tetramer approach combined with single-cell culture, we investigated the B-cell receptor (BCR) repertoire characteristics, avidity, and phenotype of donor HLA-DQ reactive B cells in a transplant recipient with end-stage donor specific antibody (DSA)-associated cardiac allograft vasculopathy while receiving maintenance immunosuppression (tacrolimus, mycophenolate mofetil, prednisone).
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!