Sabah El-Ghaiesh, MSc, Joseph P

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Presentation transcript:

Characterization of drug-specific lymphocyte responses in a patient with drug-induced liver injury Sabah El-Ghaiesh, MSc, Joseph P. Sanderson, PhD, John Farrell, MPhil, Sidonie N. Lavergne, PhD, Wing-Kin Syn, MBChB, Munir Pirmohamed, FRCP, B. Kevin Park, PhD, Dean J. Naisbitt, PhD Journal of Allergy and Clinical Immunology Volume 128, Issue 3, Pages 680-683.e5 (September 2011) DOI: 10.1016/j.jaci.2011.04.031 Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Trimethoprim stimulates lymphocytes from a patient with drug-induced liver injury. A, graphs 1 and 2, Lymphocytes were stimulated to proliferate with trimethoprim during the reaction and when the clinical signs subsided. Graph 3, IFN-γ and IL-13 secretion from trimethoprim-stimulated lymphocytes. SI, Stimulation index. B, Measurement of the frequencies of trimethoprim-specific T cells. Each symbol shows data from 1 culture. The zero value on the y-axis shows the averaged counts per minute in control cultures + 3 SDs. C, The specificity of positive cultures was confirmed by measuring titrated proliferative responses with trimethoprim. D, Trimethoprim-specific proliferation and cytokine secretion from T-cell lines (3 representative lines shown). Proliferation data represent the mean of triplicate cultures. The coefficient of variation was constantly less than 20%. Journal of Allergy and Clinical Immunology 2011 128, 680-683.e5DOI: (10.1016/j.jaci.2011.04.031) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 A, IFN-γ, TNF-α, and IL-13 secretion by cytotoxic and noncytotoxic T-cell clones after trimethoprim stimulation. B, CCR4, CCR9, CCR10, and CXCR3 expression on trimethoprim-specific T-cell clones. Receptor expression was measured by means of flow cytometry. Each dot represents an individual T-cell clone. MFI, Mean fluorescence intensity. Journal of Allergy and Clinical Immunology 2011 128, 680-683.e5DOI: (10.1016/j.jaci.2011.04.031) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Proliferation, cytolytic activity, and T-cell receptor typing of trimethoprim-responsive T-cell clones. A and B, Concentration-dependent proliferation of trimethoprim-stimulated CD4+ and CD8+ clones expressing different Vβ receptors. Fig E1, A, shows expanded dose-dependent proliferation of trimethoprim-specific clones (each symbol shows the response of an individual clone). C, Cytolytic activity of trimethoprim-stimulated T-cell clones against 51Cr-loaded antigen-presenting cells. D, Increased CD107a expression on cytotoxic and noncytotoxic T-cell clones after trimethoprim stimulation. CD107a expression was measured by means of flow cytometry. Proliferation and cytotoxicity data represent the mean of triplicate cultures. The coefficient of variation was constantly less than 20%. Journal of Allergy and Clinical Immunology 2011 128, 680-683.e5DOI: (10.1016/j.jaci.2011.04.031) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions