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Proposed models for D-AIN related to immunotherapy. In proposed model 1, immunotherapy (pembrolizumab)…
Figure 1
Proposed models for D-AIN related to immunotherapy. In proposed model 1, immunotherapy (pembrolizumab) directly induces the activation of T lymphocytes, which become sensitized against it, either on their own or via drug hapten molecules that are internalized into renal tubular cells and processed by antigen-presenting cells. These cells present the antigen to mature T lymphocytes in the renal interstitium, activating them, or they migrate to lymph nodes to present the antigen to naïve T lymphocytes, transforming them into activated T cells. In proposed model 2, immunotherapy (pembrolizumab, anti-PD1) causes previously sensitized T lymphocytes against a drug in a latent state (because of the PD1-PDL1/2 interaction) to lose their tolerance. This leads to secondary activation (via the second signal CD80/86 with CD28) and direct cytotoxic T cel–-mediated damage to renal cells expressing the antigen. D-AIN, drug-induced acute interstitial nephritis; PD1, programmed cell death protein 1; PDL1, programmed-death ligand 1.
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