Dean J. Naisbitt, PhDa, John Farrell, BSca, Gavin Wong, MBChBb, Jan p

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Presentation transcript:

Characterization of drug-specific T cells in lamotrigine hypersensitivity Dean J. Naisbitt, PhDa, John Farrell, BSca, Gavin Wong, MBChBb, Jan p.H. Depta, BScc, Charlotte C. Dodd, PhDa, Josephine E. Hopkins, BSca, Claire A. Gibney, BSca, David W. Chadwick, FRCPd, Werner J. Pichler, MDc, Munir Pirmohamed, FRCPa, B.Kevin Park, PhDa Journal of Allergy and Clinical Immunology Volume 111, Issue 6, Pages 1393-1403 (June 2003) DOI: 10.1067/mai.2003.1507 Copyright © 2003 Mosby, Inc. Terms and Conditions

Fig. 1 a and b , Proliferation of PBMCs from LTG-hypersensitive patients and controls. c, Proliferation of PBMCs from patient 1 with LTG and related compounds. Statistical analysis compares incubations with and without antigen (*P < .05). Journal of Allergy and Clinical Immunology 2003 111, 1393-1403DOI: (10.1067/mai.2003.1507) Copyright © 2003 Mosby, Inc. Terms and Conditions

Fig. 2 Cell surface expression of the skin-homing molecule CLA on LTG- and TT-specific T-cell clones. Journal of Allergy and Clinical Immunology 2003 111, 1393-1403DOI: (10.1067/mai.2003.1507) Copyright © 2003 Mosby, Inc. Terms and Conditions

Fig. 3 a, Phenotype, proliferation, and cytotoxicity of LTG-specific T-cell clones. b, Cytotoxicity was inhibited by concanamycin A, an inhibitor of perforin killing. c, Perforin was secreted by LTG-stimulated T-cell clones. d, No staining was found in incubations without T cells. Statistical analysis compares incubations with and without antigen (*P < .05). Journal of Allergy and Clinical Immunology 2003 111, 1393-1403DOI: (10.1067/mai.2003.1507) Copyright © 2003 Mosby, Inc. Terms and Conditions

Fig. 4 a, Proliferation and chemokine secretion (b and c) by LTG-specific T-cell clones. Statistical analysis was performed by comparing proliferation or chemokine release in the presence and absence of antigen (*P < .05). Journal of Allergy and Clinical Immunology 2003 111, 1393-1403DOI: (10.1067/mai.2003.1507) Copyright © 2003 Mosby, Inc. Terms and Conditions

Fig. 5 Mechanism of LTG presentation to T-cell clones. a and b, LTG is presented on HLA-DR and HLA-DQ by HLA-matched antigen-presenting cells. c and d, LTG is presented to T cells by B-LCLs in the absence of drug metabolism. e and f, LTG is presented by B-LCLs in the absence of antigen processing. Statistical analysis compares incubations with and without antigen (*P < .05). Journal of Allergy and Clinical Immunology 2003 111, 1393-1403DOI: (10.1067/mai.2003.1507) Copyright © 2003 Mosby, Inc. Terms and Conditions

Fig. 6 Proliferation of LTG-specific T-cell clones stimulated with LTG and related compounds. Colors refer to individual clones. Journal of Allergy and Clinical Immunology 2003 111, 1393-1403DOI: (10.1067/mai.2003.1507) Copyright © 2003 Mosby, Inc. Terms and Conditions

Fig. 7 Scheme depicting the chemical, cellular, and molecular pathophysiology of LTG hypersensitivity. Journal of Allergy and Clinical Immunology 2003 111, 1393-1403DOI: (10.1067/mai.2003.1507) Copyright © 2003 Mosby, Inc. Terms and Conditions