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

Sasan Jalili, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Ryan R. Hosn, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Wei-Che Ko, Department of Dermatology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.
Khashayar Afshari, Department of Dermatology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.
Ashok Kumar Dhinakaran, Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
Namit Chaudhary, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Laura Maiorino, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Nazgol Haddadi, Department of Dermatology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.
Anusha Nathan, Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, 02139, USA.
Matthew A. Getz, Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, 02139, USA.
Gaurav D. Gaiha, Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, 02139, USA.
Mehdi Rashighi, Department of Dermatology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.
John E. Harris, Department of Dermatology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.
Paula T. Hammond, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Darrell J. Irvine, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.

Document Type

Article

Publication Title

medRxiv : the preprint server for health sciences

Abstract

Detecting antigen-specific lymphocytes is crucial for immune monitoring in the setting of vaccination, infectious disease, cancer, and autoimmunity. However, their low frequency and dispersed distribution across lymphoid organs, peripheral tissues, and blood pose challenges for reliable detection. To address this issue, we developed a strategy exploiting the functions of tissue-resident memory T cells (Ts) to concentrate target circulating immune cells in the skin and then sample these cells non-invasively using a microneedle (MN) skin patch. Ts were first induced at a selected skin site through initial sensitization with a selected antigen. Subsequently, these Ts were restimulated by intradermal inoculation of a small quantity 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 models of vaccination, we show that application of MN patches coated with an optimized hydrogel layer for cell and fluid sampling to this skin site allowed effective isolation of thousands of live antigen-specific lymphocytes as well as innate immune cells. In a human subject with allergic contact dermatitis, stimulation of Ts with allergen followed by MN patch application allowed the recovery of diverse lymphocyte populations that were absent from untreated skin sites. These results suggest that T restimulation coupled with microneedle patch sampling can be used to obtain a window into both local and systemic antigen-specific immune cell populations in a noninvasive manner that could be readily applied to a wide range of disease or vaccination settings.

DOI

10.1101/2025.03.17.25324099

Publication Date

3-21-2025

Identifier

40166546 (pubmed); PMC11957092 (pmc); 10.1101/2025.03.17.25324099 (doi); 2025.03.17.25324099 (pii)

This document is currently not available here.

Share

COinS