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Graft-Specific Regulatory T Cells for Long-Lasting, Local Tolerance Induction.
Cells
July 2024
Department of Gastroenterology, Hepatology, Infectious Diseases & Endocrinology, Hannover Medical School, 30625 Hannover, Germany.
Background: Solid organ transplantation is hindered by immune-mediated chronic graft dysfunction and the side effects of immunosuppressive therapy. Regulatory T cells (Tregs) are crucial for modulating immune responses post-transplantation; however, the transfer of polyspecific Tregs alone is insufficient to induce allotolerance in rodent models.
Methods: To enhance the efficacy of adoptive Treg therapy, we investigated different immune interventions in the recipients.
CD28 Blockade Induces Alloantigen-Specific Immune Tolerance but Preserves T-Cell Pathogen Reactivity.
Front Immunol
September 2017
Tumor Immunology, Children's Cancer Research Institute (CCRI), St. Anna Kinderkrebsforschung e.V., Vienna, Austria.
Donor T-cells contribute to reconstitution of protective immunity after allogeneic hematopoietic stem cell transplantation (HSCT) but must acquire specific tolerance against recipient alloantigens to avoid life-threatening graft-versus-host disease (GvHD). Systemic immunosuppressive drugs may abrogate severe GvHD, but this also impedes memory responses to invading pathogens. Here, we tested whether blockade of CD28 co-stimulation can enable selective T-cell tolerization to alloantigens by facilitating CD80/86-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) signaling.
View Article and Find Full Text PDFIncomplete clonal deletion as prerequisite for tissue-specific minor antigen tolerization.
JCI Insight
May 2016
Section of Transplantation Immunology, Department of Surgery, and.
Central clonal deletion has been considered the critical factor responsible for the robust state of tolerance achieved by chimerism-based experimental protocols, but split-tolerance models and the clinical experience are calling this assumption into question. Although clone-size reduction through deletion has been shown to be universally required for achieving allotolerance, it remains undetermined whether it is sufficient by itself. Therapeutic Treg treatment induces chimerism and tolerance in a stringent murine BM transplantation model devoid of myelosuppressive recipient treatment.
View Article and Find Full Text PDFAlloimmunity and Tolerance in Corneal Transplantation.
J Immunol
May 2016
Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114
Corneal transplantation is one of the most prevalent and successful forms of solid tissue transplantation. Despite favorable outcomes, immune-mediated graft rejection remains the major cause of corneal allograft failure. Although low-risk graft recipients with uninflamed graft beds enjoy a success rate ∼90%, the rejection rates in inflamed graft beds or high-risk recipients often exceed 50%, despite maximal immune suppression.
View Article and Find Full Text PDFLung-Restricted Antibodies Mediate Primary Graft Dysfunction and Prevent Allotolerance after Murine Lung Transplantation.
Am J Respir Cell Mol Biol
October 2016
4 Norton Thoracic Institute, St. Joseph's Hospital, Phoenix, Arizona.
Over one-third of lung recipients have preexisting antibodies against lung-restricted antigens: collagen (Col) type V and K-α1 tubulin (KAT). Although clinical studies have shown association of these antibodies with primary graft dysfunction (PGD), their biological significance remains unclear. We tested whether preexisting lung-restricted antibodies can mediate PGD and prevent allotolerance.
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