What is already known: Constipation, inflammation and intestinal obstructive episodes are major health problems in cystic fibrosis patients What this study adds: This study determines the ability of three FDA-approved drugs to increase gut fluidity and alkalinity in mice that express no CFTR protein or that express the F508del mutant protein and studies the mechanism of action. Clinical significance: These results pave the way for clinical trials to improve gut fluidity and reduce obstructive episodes in CF patients.
These data suggest that signals triggered by PD-1-PD-L1 interaction interfere with activation pathways involved in the induction of cellular and antibody-mediated immune responses to xenografts in vivo. Targeting of PD-1 and/or PD-L1 may be a promising approach for immune modulation after xenotransplantation.
We have shown that although ADAP is dispensable for the rejection of allografts, ADAP function plays an important role for the efficacy of graft rejection. ADAP's main function appears to affect the induction phase of the immune response.
Background
Differences in quality and strength of immune responses between individuals are mainly due to polymorphisms in major histocompatibility complex (MHC) molecules. Focusing on MHC class‐II, we asked whether the intensity of human anti‐pig T‐cell responses is influenced by genetic variability in the human HLA‐DRB1 and/or the porcine SLA‐DRB1 locus.
Methods
ELISpot assays were performed using peripheral blood mononuclear cells (PBMCs) from 62 HLA‐DRB1‐typed blood donors as responder and the porcine B cell line L23 as stimulator cells. Based on the frequency of IFN‐γ‐secreting cells, groups of weak, medium, and strong responder individuals were defined. Mixed lymphocyte reaction (MLR) assays were performed to study the stimulatory capacity of porcine PBMCs expressing different SLA‐DRB1 alleles.
Results
Concerning the MHC class‐II configuration of human cells, we found a significant overrepresentation of HLA‐DRB1*01 alleles in the medium/strong responder group as compared to individuals showing weak responses to stimulation with L23 cells. Evaluation of the role of MHC class‐II variability in porcine stimulators revealed that cells expressing SLA‐DRB1*06 alleles triggered strong proliferation in approximately 70% of humans. Comparison of amino acid sequences indicated that strong human anti‐pig reactivity may be associated with a high rate of similarity between human and pig HLA/SLA‐DRB1 alleles.
Conclusion
Variability in human and porcine MHC determines the intensity of individual human anti‐pig T‐cell responses. MHC typing and cross‐matching of prospective recipients of xenografts and donor pigs could be relevant to select for donor‐recipient combinations with minimal anti‐porcine immunity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.