BACKGROUND: One to three percent of patients exposed to intravenously injected iodinated contrast media (CM) develop delayed hypersensitivity reactions. Positive patch test reactions, immunohistological findings, and CM-specific proliferation of T cells in vitro suggest a pathogenetic role for T cells. We have previously demonstrated that CM-specific T cell clones (TCCs) show a broad range of cross-reactivity to different CM. However, the mechanism of specific CM recognition by T cell receptors (TCRs) has not been analysed so far. OBJECTIVE: To determine how T cells specifically recognize CM. METHODS: CM-specific TCCs were generated from human blood of three CM-allergic patients and a specific TCR was transfected into a mouse T cell hybridoma. Functional analysis such as proliferation assays, IL-2 secretion assays, and calcium influx experiments were performed using irradiated, glutaraldehyde-fixed, CM-pre-incubated, human leucocyte antigen (HLA)-DR-matched or -mismatched antigen-presenting cells (APCs), and HLA-blocking antibodies. RESULTS: We identified two mechanisms of T cell stimulation: some TCCs and the transfectant reacted to CM independent of uptake by APCs because proliferation/IL-2 secretion occurred in the presence of glutaraldehyde-fixed APCs, and intracellular calcium increased within seconds after drug addition. Other TCCs required functional APCs, compatible with uptake and presentation of CM on MHC-class II molecules, as implied by three findings: (1) glutaraldehyde fixation of APCs abrogated presentation; (2) CM could not be washed away from CM-pre-incubated APCs; and (3) the optimal pulsing time was 10-20 h. Because allogeneic, MHC-matched, CM-pulsed APCs could induce proliferative responses as well, the ability of CM uptake and presentation is not unique to APCs from patients with CM-induced delayed hypersensitivity. CONCLUSION: Our data suggest that CM may be stimulatory for T cells either by direct binding to the MHC-TCR complex or by binding after uptake and processing by APCs. This questions the assumed inert nature of CM.
BACKGROUND: One to three percent of patients exposed to intravenously injected iodinated contrast media (CM) develop delayed hypersensitivity reactions. Positive patch test reactions, immunohistological findings, and CM-specific proliferation of T cells in vitro suggest a pathogenetic role for T cells. We have previously demonstrated that CM-specific T cell clones (TCCs) show a broad range of cross-reactivity to different CM. However, the mechanism of specific CM recognition by T cell receptors (TCRs) has not been analysed so far. OBJECTIVE: To determine how T cells specifically recognize CM. METHODS: CM-specific TCCs were generated from human blood of three CM-allergicpatients and a specific TCR was transfected into a mouse T cell hybridoma. Functional analysis such as proliferation assays, IL-2 secretion assays, and calcium influx experiments were performed using irradiated, glutaraldehyde-fixed, CM-pre-incubated, human leucocyte antigen (HLA)-DR-matched or -mismatched antigen-presenting cells (APCs), and HLA-blocking antibodies. RESULTS: We identified two mechanisms of T cell stimulation: some TCCs and the transfectant reacted to CM independent of uptake by APCs because proliferation/IL-2 secretion occurred in the presence of glutaraldehyde-fixed APCs, and intracellular calcium increased within seconds after drug addition. Other TCCs required functional APCs, compatible with uptake and presentation of CM on MHC-class II molecules, as implied by three findings: (1) glutaraldehyde fixation of APCs abrogated presentation; (2) CM could not be washed away from CM-pre-incubated APCs; and (3) the optimal pulsing time was 10-20 h. Because allogeneic, MHC-matched, CM-pulsed APCs could induce proliferative responses as well, the ability of CM uptake and presentation is not unique to APCs from patients with CM-induced delayed hypersensitivity. CONCLUSION: Our data suggest that CM may be stimulatory for T cells either by direct binding to the MHC-TCR complex or by binding after uptake and processing by APCs. This questions the assumed inert nature of CM.
Authors: Sabah El-Ghaiesh; Manal M Monshi; Paul Whitaker; Rosalind Jenkins; Xiaoli Meng; John Farrell; Ayman Elsheikh; Daniel Peckham; Neil French; Munir Pirmohamed; B Kevin Park; Dean J Naisbitt Journal: J Pharmacol Exp Ther Date: 2012-02-27 Impact factor: 4.030
Authors: Sarah Nicolai; Marcin Wegrecki; Tan-Yun Cheng; Elvire A Bourgeois; Rachel N Cotton; Jacob A Mayfield; Gwennaëlle C Monnot; Jérôme Le Nours; Ildiko Van Rhijn; Jamie Rossjohn; D Branch Moody; Annemieke de Jong Journal: Sci Immunol Date: 2020-01-03
Authors: Paul Whitaker; Xiaoli Meng; Sidonie N Lavergne; Sabah El-Ghaiesh; Manal Monshi; Caroline Earnshaw; Daniel Peckham; Jimmy Gooi; Steve Conway; Munir Pirmohamed; Rosalind E Jenkins; Dean J Naisbitt; B Kevin Park Journal: J Immunol Date: 2011-05-23 Impact factor: 5.422