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- W4313381534 abstract "Abstract Background Many studies have focused on finding a correlation between the responsiveness to immune checkpoint (IC) therapies and the expression level of IC markers. Here, we report the studies on the expression of co-inhibitory molecules on healthy donor peripheral mononuclear cells (PBMC). We co-cultured PBMCs from different donors with recall antigen peptide to analyze the responses to PD-1 blockade antibody treatment. We have used our previously reported optimized recall antigen assay in which the expanded antigen specific CD8+ T cells (TET+) were measured as a readout after the peptide stimulation. Interestingly, the IgG4 appears to reduce the TET+ cell population. To further study this potential effect of IgG4, we conducted a series of immune-profiling studies by comparing TET+ gated and TET− CD8+ gated T cells. Results and conclusion Healthy donor PBMCs were stimulated with recall peptide alone, or peptide plus either PD-1 blockade, or IgG4 and evaluated the PD-1, PD-L1, Tim-3, and Lag-3 expressions in either T cells or in monocytes. We then compared such expressions in TET+ and TET− CD8+ T cells. Unexpectedly, IgG4 isotype control treatment was associated with upregulated PD-L1 expression only in the TET+ CD8+ T cells. To confirm whether the decrease of TET+ population in our assay was caused by the up regulation of PD-L1, we blocked the PD-1 signal transduction pathway by treating the cells with a validated PD-1 blocking antibody. As a result of PD-1 blockade, the expansion of TET+ cell population was recovered by anti-PD-1 blocking treatment. Taken together, these results suggest that IgG4 treatment with recall peptide up regulates PD-L1 expression and therefore reduces the expansion of antigen specific CD8+ T cells in some donors." @default.
- W4313381534 created "2023-01-06" @default.
- W4313381534 creator A5049686588 @default.
- W4313381534 creator A5087651357 @default.
- W4313381534 date "2019-05-01" @default.
- W4313381534 modified "2023-09-25" @default.
- W4313381534 title "Regulation of PD-L1 expression in stimulated antigen specific CD8+ T cells by immunoglobulin 4 (IgG4)" @default.
- W4313381534 doi "https://doi.org/10.4049/jimmunol.202.supp.195.35" @default.
- W4313381534 hasPublicationYear "2019" @default.
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