Donor hemopoietic cell engraftment is considered to be an indicator of allograft tolerance. We depleted chimerism with cells specifically presensitized to the bone marrow donor to investigate its role in mixed chimera-induced tolerance. Three experimental models were used: model A, B10.A cells presensitized to B6 (a anti-b cells) were injected into (B6 x D2)F(1) --> B10.A mixed chimeras grafted with DBA/2 skin; model B, anti-B6 presensitized cells prepared in DBA/2 --> B10.A mixed chimeras, thus unresponsive to DBA/2 (a anti-b/tol-d cells), were injected into (B6 x D2)F(1) --> B10.A mixed chimeras grafted with DBA/2 skin; and model C, (BALB/c x B6)F(1) cells presensitized to CBA (d/b anti-k cells) were injected into (B6 x CBA)F(1) --> BALB/c mixed chimeras grafted with B6 skin. Skin was grafted on day 30. Injection of each cell type before skin grafting abolished hemopoietic cell engraftment and prevented allograft acceptance. Injection of presensitized cells after skin grafting resulted in different outcomes depending on the models. In model A, injection of a anti-b cells completely depleted chimerism and caused allograft rejection. In model B, injection of a anti-b/tol-d cells markedly reduced, but did not deplete, peripheral chimerism and maintained skin allograft survival. In model C, d/b anti-k cells reduced chimerism to the background levels but failed to cause graft rejection, probably due to persistence of injected cells which share MHC with skin grafts. Together, the results show that presence of chimeric donor cells is essential in both the induction and maintenance phases of tolerance induced by mixed chimerism.
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http://dx.doi.org/10.4049/jimmunol.172.3.1444 | DOI Listing |
Pediatr Crit Care Med
January 2025
Paediatric Intensive Care Unit, Great Ormond Street Hospital for Children NHS Foundation Trust and NIHR Biomedical Research Centre, London, United Kingdom.
Objectives: A conservative oxygenation strategy is recommended in adult and pediatric guidelines for the management of acute respiratory distress syndrome to reduce iatrogenic lung damage. In the recently reported Oxy-PICU trial, targeting peripheral oxygen saturations (Spo2) between 88% and 92% was associated with a shorter duration of organ support and greater survival, compared with Spo2 greater than 94%, in mechanically ventilated children following unplanned admission to PICU. We investigated whether this benefit was greater in those who had severely impaired oxygenation at randomization.
View Article and Find Full Text PDFCells
December 2024
Departments of Blood and Marrow Transplant, Royal Manchester Children's Hospital, Manchester M13 9WL, UK.
Myeloid chimerism better reflects donor stem cell engraftment than whole-blood chimerism in assessing graft function following allogeneic hematopoietic stem cell transplant (HCT). We describe our experience with 130 patients aged younger than 18 years, treated with allogeneic HCT using bone marrow or PBSC from HLA-matched donors for non-malignant diseases, whose pre-transplant conditioning therapy included alemtuzumab and who were monitored with lineage-specific chimerism after transplant. At 6 years post-transplant, overall survival (OS) was 91.
View Article and Find Full Text PDFMedicine (Baltimore)
December 2024
Shangrao City Maternal and Child Health Hospital, Shangrao, China.
This study was aimed to investigate the performance of chromosomal microarray analysis (CMA) in prenatal diagnosis compared with traditional karyotyping analysis. Both CMA and karyotyping analyses were performed to detect the karyotypes in the amniotic fluid of 491 pregnant women who got prenatal diagnosis at the Center of Prenatal Diagnosis of Shangrao (China) during January 2019 to April 2021. After excluding 2 samples in the CMA analysis and 2 samples in the karyotyping analysis which were failed in detection, the remaining 487 amniotic fluid samples were detected.
View Article and Find Full Text PDFJ Am Chem Soc
December 2024
School of Applied and Interdisciplinary Sciences, Indian Association for the Cultivation of Science, Kolkata 700 032, India.
Phosphorodiamidate Morpholino Oligonucleotides (PMOs) have been well established in the milieu of FDA-approved oligonucleotide-based drugs in the past decade. Given their relevance in antisense therapeutics, a DNA/RNA synthesizer-compatible modular synthesis protocol of PMOs is long awaited to explore next-generation PMO chimeras with other therapeutically proven oligonucleotide backbones. Herein, we demonstrate a streamlined 5' → 3'phosphoramidite approach for the synthesis of PMOs using -butyl-protected 5'-morpholino phosphoramidites, which were synthesized from 5'-OH morpholino monomers derived from commercially available ribonucleosides.
View Article and Find Full Text PDFAm J Respir Cell Mol Biol
December 2024
Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina.
IL-4 and IL-13 play a critical role in allergic asthma pathogenesis via their common receptor IL-4Rα. However, the cell-specific role of IL-4Rα in mixed allergen (MA)-induced allergic asthma has remained unclear. Therefore, we aimed to identify the cell-specific contribution of IL-4Rα signaling in the manifestation of various pathological outcomes in mice with allergic airway disease.
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