Suppression of IGRP-specific CD8 T cells following induction of tolerance to a Hybrid Insulin Peptide CD4 neoepitope
نویسندگان
چکیده
Abstract An autoimmune-mediated death of insulin-producing beta cells, orchestrated by effector CD4 and CD8 T cells that recognize islet antigens, results in Type 1 Diabetes. A dominant autoantigen the NOD mouse model autoimmune diabetes is a neoepitope termed 2.5 Hybrid Insulin Peptide (2.5HIP). By delivering 2.5HIP as an antigen-specific immunotherapy on tolerogenic PLG-nanoparticles, grafts diabetic mice survived longer cytokine production autoreactive was suppressed, including well-studied IGRP tetramer+ (tet+) cells. Using both transplant recipients prediabetic treated with nanoparticles, we examined mechanisms peripheral tolerance induction to impact function Following 2.5HIP, there increase dysfunctional surface marker expression (PD1+ TIM3+) tet+ spleen mice. Along decrease function, observed fraction Treg Tr1 expressing IL10 islets, spleen, draining lymph nodes tolerized Concurrently, accumulated were less able traffic infiltrate islets. Of entered fewer cytolytic CX 3CR1 +effector The robust functional may provide potential mechanism for accumulation node explain their inefficient trafficking into, within, islets following induction. NIH - T32 5T32DK120520-03, R01 2R01DK081166-11) JDRF 2-SRA-2020-907-S-B
منابع مشابه
Induction of T Regulatory Subsets from Naïve CD4+ T Cells after Exposure to Breast Cancer Adipose Derived Stem Cells
Background: Adipose derived stem cells (ASCs) provoke the accumulation and expansion of regulatory T cells, leading to the modulation of immune responses in tumor microenvironment. Objective: To assess the effect of tumoral ASCs on the trend of regulatory T cells differentiation. Methods: Peripheral blood naïve CD4+ T cells were co-cultured with ASCs derived from breast cancer or normal breast ...
متن کاملSemimature Dendritic Cells Tolerance and CD8 T Cell Immunity by Simultaneous Induction of CD4 T Cell
متن کامل
Simultaneous induction of CD4 T cell tolerance and CD8 T cell immunity by semimature dendritic cells.
Previous studies suggested that depending on their maturation state, dendritic cells (DC) could either induce T cell tolerance (immature and semimature DC) or T cell activation (mature DC). Pretreatment of C57BL/6 mice with encephalitogenic myelin oligodendrocyte glycoprotein (MOG)(35-55) peptide-loaded semimature DC protected from MOG-induced autoimmune encephalomyelitis. This protection was m...
متن کاملTNF-mediated toxicity after massive induction of specific CD8+ T cells following immunization of mice with a tumor-specific peptide.
We immunized mice with antigenic peptide P815E, which is presented by H-2K(d) and recognized by tumor-specific CTL raised against P815 tumor cells. This peptide is encoded by the ubiquitously expressed gene MsrA and carries a mutated residue conferring tumor specificity. Unexpectedly, we observed a severe toxicity occurring in the early hours after the third injection, resulting in the death of...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Journal of Immunology
سال: 2023
ISSN: ['1550-6606', '0022-1767']
DOI: https://doi.org/10.4049/jimmunol.210.supp.238.04