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Elucidating CD4+ and CD8+ T-cell involvement in patients with vancomycin-induced DRESS.

Joshua Gardner1, Silvia Martinez-Rivera2, James Line1

  • 1Department of Pharmacology and Therapeutics, Centre for Drug Safety Science, The University of Liverpool, Liverpool L69 3GE, United Kingdom.

Toxicological Sciences : an Official Journal of the Society of Toxicology
|May 27, 2025
PubMed
Summary

Vancomycin-induced DRESS involves both CD4+ and CD8+ T-cells, which are activated by direct drug interactions. This study clarifies the dual T-cell role in DRESS pathogenesis for better diagnosis and prediction.

Keywords:
DRESSHLAT-lymphocytescytokinesdrug hypersensitivityvancomycin

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Area of Science:

  • Immunology
  • Pharmacology
  • Genetics

Background:

  • Vancomycin-induced DRESS is a severe reaction linked to HLA-A*32:01.
  • The precise mechanisms of DRESS pathogenesis are not fully understood.
  • T-cell involvement has been suggested but requires deeper mechanistic insight.

Purpose of the Study:

  • To investigate the role of CD4+ and CD8+ T-cells in vancomycin-induced DRESS.
  • To functionally characterize vancomycin-specific T-cell clones from hypersensitive patients.
  • To elucidate the mechanisms underlying T-cell activation in DRESS.

Main Methods:

  • Generation of vancomycin-responsive CD4+ and CD8+ T-cell clones (TCCs) from patients.
  • Assessment of TCC functionality via [3H]-thymidine proliferation assays.
  • Cytokine analysis using intracellular cytokine staining, ELISpot, and LEGENDplex immunoassays.

Main Results:

  • Successfully generated CD4+ and CD8+ vancomycin-responsive TCCs from DRESS patients.
  • Identified CD45RO+ memory T-cells as the primary activated population.
  • Both CD4+ and CD8+ T-cells released key cytokines (IFN-γ, IL-5, IL-13) and cytotoxic molecules (granzyme B, perforin).

Conclusions:

  • Vancomycin-responsive T-cells are activated through direct drug interaction and HLA class I/II antigen presentation.
  • This study provides in vitro evidence for a dual role of CD4+ and CD8+ T-cells in vancomycin-induced DRESS pathogenesis.
  • Findings support the importance of T-cell specificity and HLA-A*32:01 in DRESS development.