107. CD8+ T cells are important for recovery from chemotherapy-induced neuropathy in mice

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is the major dose-limiting toxicity for cancer treatment. In this study we investigated the contribution of T cells in the course of CIPN. Wild type (WT; C57Bl6J) and T cell-deficient mice (Rag1−/−) were treated with chemotherapy (paclitaxel) and mechanical hyperalgesia was measured. Mechanical hyperalgesia developed immediately following treatment in WT and Rag1−/− mice. In WT mice paclitaxel-induced mechanical hyperalgesia resolved 14 days after treatment. However, in Rag1−/− mice mechanical hyperalgesia persisted for more than 21 days. When T cells (CD3+) were transferred into Rag1−/− mice paclitaxel-induced mechanical hyperalgesia resolved by 14 days. These data demonstrate that T cells are critical for resolution from CIPN. Paclitaxel administration has been shown to damage peripheral sensory neuron cell bodies located in dorsal root ganglia (DRGs). Immunohistochemistry analysis revealed that the transferred T cells localized to (DRGs) in Rag1−/− mice. Next, we investigated if a single T cell subset was responsible for resolution from CIPN. Transfer of CD8+ T cells into Rag1−/− mice was sufficient to normalize resolution of paclitaxel-induced mechanical hyperalgesia by 14 days. In contrast when Rag1−/− mice were injected with CD4+ T cells mechanical hyperalgesia persisted for up to 21 days. How CD8+ T cells regulate resolution from CIPN is under investigation, nevertheless this is the first study to our knowledge to identify a beneficial role for CD8+ T cells in CIPN.