Multiple drug hypersensitivity: normal Treg cell function but enhancedin vivoactivation of drug-specific T cells

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Abstract

To cite this article:

Daubner B, Groux-Keller M, Hausmann OV, Kawabata T, Naisbitt DJ, Park BK, Wendland T, Lerch M, Pichler WJ. Multiple drug hypersensitivity: normal Treg cell function but enhanced in vivo activation of drug-specific T cells. Allergy 2012; 67: 58–66.

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+ CD25bright 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+ CD25dim T cell fraction and showed enhanced CD38 and PD-1 expression, while those from monoallergic patients reside in the resting CD4+ CD25neg 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.

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