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- W1963991024 abstract "Vasoactive intestinal peptide (VIP) can lead to the generation of regulatory dendritic cells (DC). In this study, we used DC and T-cells from VIP-knockout (VIP-KO) mice to investigate the effects of VIP on allogeneic and anti-viral immune responses in transplant recipients. 5×106 BM and 1, 3, 8×106 splenocytes (SP) from VIP-KO and WT donors, single VIP-KO donors, single WT donors, or single VIP-heterozygous donors were transplanted in B6→B10BR alloBMT and B6→B6 synBMT models. Survival and GvHD were assessed. VIP-KO mice, WT littermates, and recipients were infected with 5×104 PFU murine cytomegalovirus (mCMV) and T cell response to viral antigen was measured by flow cytometry for mCMV peptide-MHC class I-tetramer+ CD8+ T-cells at day 0, 3, 7, 10, and day 15 post infection or 80, 83, 87 and 101 days post-transplant (infection at day 80 post-transplant). Day 15 post mCMV challenge, VIP-KO and WT mice were euthanized. DC and T-cells were purified from BM and SP by FACS and MACS, respectively. 2×105/mL DC treated with 1×104 PFU mCMV peptide-expressing Listeria-CMV construct and incubated with 2×106/mL T-cells at 37 °C. Cultured 3 days and 7 days, cells were harvested and analyzed with DC and T-cell surface marker, tetramer, and intracellular cytokines by flow cytometry. allogeneic recipients of VIP-KO BM and VIP-KO SP developed more GvHD than recipients of WT grafts using a lower dose of donor SP (1×106), while there was no difference in survival. The GvHD scores and the percentage of survival showed no difference among other syngeneic or allogeneic BMT settings.The specific anti-viral immunity was similar among the non-transplanted VIP-KO mice, and allogeneic and syngeneic transplant recipients of VIP-KO donor cells. 3 and 7 days post culture, VIP-KO DC expressed higher-level of CD80, MHC-II and lower-level of PD-L1, VIP-KO T-cells had higher-level of tetramer+ CD8+ T-cells and intracellular IFN-γ, lower-level of IL-4 and IL-5, PD1, and ICOS. Taken together, these observations suggest that VIP expressed on immune cells suppresses anti-viral immune responses and Th1 polarization. The anti-viral immune responses of VIP-KO immune cells were independent allogeneic immunity; VIP expressed by neurocrine cells in WT recipients did not compensate for the lack of VIP in mice transplanted with VIP-KO cells. Modulation of the VIP pathway is a novel method to regulate post-transplant immunity allogeneic transplant recipients." @default.
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- W1963991024 date "2010-02-01" @default.
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- W1963991024 title "The Absence Of Vasoactive Intestinal Peptide Augments Allo-Reactivity And The Anti-Viral Response In A Bone Marrow Transplant Setting" @default.
- W1963991024 doi "https://doi.org/10.1016/j.bbmt.2009.12.212" @default.
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