Publications by authors named "G Tilly"

The use of immunosuppressive treatment is required to prevent rejection events, even a long time after kidney transplantation despite rare recipients achieving long-term graft stability without the need for immunosuppressive treatment, called operationally tolerant patients (TOLs). We comprehensively investigate the immune system of long-term IS recipients (LTTs) and TOLs to highlight their shared and unique immune features. Blood immune cell phenotyping was performed by spectral cytometry.

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Article Synopsis
  • - Buffalo/Mna rats develop nephrotic syndrome that can recur after kidney transplantation, and the drug LF15-0195 may help treat both the initial syndrome and post-transplantation issues by promoting regulatory T cells.
  • - The study used various techniques to analyze kidney samples from Buff/Mna rats at different disease stages, showing that LF15-0195 treatment restored the foot process architecture of podocytes, which could correlate with reduced proteinuria.
  • - Although LF15-0195 didn't significantly change the mRNA or protein levels of several specific podocyte proteins, it improved their distribution within the glomeruli, indicating that the drug might work through immune modulation and potentially also improve the cytoskeleton of endothelial cells under stress
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  • Human Granzyme B (GZMB) regulatory B cells, known as Bregs, can suppress CD4+ effector T cells, and they are easily induced in lab settings for potential use in cell therapy.
  • Single-cell transcriptomics revealed that induced GZMB+Bregs uniquely express 149 different genes related to T cell proliferation and activation, demonstrating their significant inhibitory effects on T cell functions.
  • The study identifies Lymphotoxin alpha (LTA) as a new ligand that enhances GZMB expression in Bregs and contributes to their suppressive abilities, although the detailed mechanism of how LTA and GZMB work together in these cells still needs further investigation.
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Introduction: The human immune system contains cells with either effector/memory or regulatory functions. Besides the well-established CD4+CD25hiCD127lo regulatory T cells (Tregs), we and others have shown that B cells can also have regulatory functions since their frequency and number are increased in kidney graft tolerance and B cell depletion as induction therapy may lead to acute rejection. On the other hand, we have shown that CD28-CD8+ T cells represent a subpopulation with potent effector/memory functions.

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Background: The mechanisms regulating CD8 T cell migration to nonlymphoid tissue during inflammation have not been fully elucidated, and the migratory properties of effector memory CD8 T cells that re-express CD45RA (TEMRA CD8 T cells) remain unclear, despite their roles in autoimmune diseases and allotransplant rejection.

Methods: We used single-cell proteomic profiling and functional testing of CD8 T cell subsets to characterize their effector functions and migratory properties in healthy volunteers and kidney transplant recipients with stable or humoral rejection.

Results: We showed that humoral rejection of a kidney allograft is associated with an accumulation of cytolytic TEMRA CD8 T cells in blood and kidney graft biopsies.

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