Leveraging tissue-resident memory T cells for non-invasive immune monitoring via microneedle skin patches

Detecting antigen-specific lymphocytes is crucial for immune monitoring in vaccination, infection, cancer and autoimmunity. However, their low frequency and dispersed distribution make reliable detection challenging. We developed a strategy exploiting the functions of tissue-resident memory T cells (T_RMs) to locally concentrate target circulating immune cells in the skin, enabling their non-invasive sampling using a microneedle (MN) skin patch. T_RMs were first induced by antigen sensitization and subsequently restimulated by intradermal inoculation of the same antigen to trigger the 'alarm' and immune recruitment functions of these cells, leading to accumulation of antigen-specific T cells from the circulation over several days. In mouse vaccination models, MN patches with optimized hydrogel coatings effectively isolated thousands of live antigen-specific lymphocytes and innate immune cells. In a human participant with allergic contact dermatitis, allergen-induced T_RM stimulation followed by MN application recovered diverse lymphocyte populations absent from untreated skin sites. These results establish T_RM restimulation coupled with MN sampling as a non-invasive platform to monitor both local and systemic antigen-specific immune responses across disease or vaccination settings.