Multiple drug hypersensitivity: role of T regulatory cells (55.15)

• Published in: The Journal of immunology (1950) 2011-04, Vol.186 (1_Supplement), p.55-55.15
• Main Authors: Daubner, Barbara, Groux-Keller, Monika, Kawabata, Thomas, Naisbitt, Dean J., Park, Kevin B., Thomas, Wendland, Marianne, Lerch, Pichler, Werner J.
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.186.Supp.55.15

Introduction: Up to 10% of patients with severe immune-mediated drug hypersensitivity tend to develop multiple drug hypersensitivities (MDH), and react clinically and immunologically to various drugs. Objective: Evaluating the role of T regulatory (T reg) cells in drug reactions and developing an improved clinical and immunological definition of MDH. Methods: T cell reactivity to various drugs was assessed by expression analysis of activation markers and cross-reactivity of drug specific T cell clones to various drugs was analyzed. The role of T regs (Foxp3+/CD25high) was analyzed functionally in T reg depletion assays. The phenotype of reacting T cells was characterized by analysis of activation and cell exhaustion markers. Results: T regs from MDH patients are functionally highly active and suppress T cell proliferation similar to T regs from monoallergic patients and healthy controls. Removal of T regs enhances the reactivity to involved drugs, but does not facilitate an immune response to not exposed drugs in vitro. Drug reactive T cells from monoallergic patients reside in the resting CD4+CD25neg T cell fraction while in MDH patients they reside in an in vivo activated cell fraction (CD4+/CD25dim/CD38+/HLA-DR+/PD-1+). Conclusion: T regs are able to regulate drug specific immune responses. In MDH patients, the drug reactive T cells are contained in a pre-activated cell fraction. This may enhance their responsiveness to drugs and thus explain MDH.