Multiple drug hypersensitivity: normal Treg cell function but enhanced in vivo activation of drug-specific T cells.

Abstract

BACKGROUND:

  Up to 10% of patients with severe immune-mediated drug hypersensitivity reactions have tendencies to develop multiple drug hypersensitivities (MDH). The reason why certain individuals develop MDH and the underlying pathomechanism are unclear. We investigated different T cell subpopulations in MDH patients and compared them with patients allergic to a single drug and with healthy controls (HC).

METHODS:

  We analyzed the in vitro reactivity of peripheral blood mononuclear cells from MDH patients (n=7), patients with hypersensitivity to a single drug (monoallergic, n=6), and healthy controls (HD) (n=6) to various drugs (mainly antibiotics and antiepileptics). By depleting and selectively re-adding CD4(+)  CD25(bright) T cells (T regulatory cells, Treg), their effect on drug-specific T cell reactivity was analyzed. The phenotype of reacting T cells was determined ex vivo by staining for markers of activation (CD38) and cell exhaustion (PD-1).

RESULTS:

  No functional deficiency of Treg cells was observed in all drug-allergic patients. Drug-reactive T cells from MDH patients were found in the CD4(+) CD25(dim) T cell fraction and showed enhanced CD38 and PD-1 expression, while those from monoallergic patients reside in the resting CD4(+)  CD25(neg) T cell fraction.

CONCLUSION:

  In patients with MDH, the drug-reactive T cells are contained in an in vivo pre-activated T cell fraction. Therefore, they may show a lower threshold for activation by drugs. The reason for this in vivo T cell pre-activation needs further investigations.

• Authors: B Daubner, M Groux-Keller, O V Hausmann, T Kawabata, D J Naisbitt, B K Park, T Wendland, M Lerch, W J Pichler
• Journal: Allergy (Allergy) Vol. 67 Issue 1 Pg. 58-66 (Jan 2012) ISSN: 1398-9995 [Electronic] Denmark
• PMID: 21933197 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 John Wiley & Sons A/S.

Topics

• Cell Separation
• Cells, Cultured
• Drug Hypersensitivity (immunology)
• Flow Cytometry
• Humans
• Immunomagnetic Separation
• Immunophenotyping
• Lymphocyte Activation (immunology)
• T-Lymphocyte Subsets (immunology)
• T-Lymphocytes, Regulatory (immunology)