Processing-dependent and -independent pathways for recognition of iodinated contrast media by specific human T cells

作者：Keller M^*; Lerch M; Britschgi M; Tache V; Gerber B O; Luethi M; Lochmatter P; Kanny G; Bircher A J; Christiansen C; Pichler W J

来源：Clinical and Experimental Allergy, 2010, 40(2): 257-268.

DOI：10.1111/j.1365-2222.2009.03425.x

• allergy
• antigen presentation
• processing
• cell activation
• cell proliferation
• human
• T cell receptors
• T cells

P>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.
Cite this as: M. Keller, M. Lerch, M. Britschgi, V. Tache, B. O. Gerber, M. Luthiuthi, P. Lochmatter, G. Kanny, A. J. Bircher, C. Christiansen and W. J. Pichler, Clinical & Experimental Allergy, 2010 (40) 257-268.

• 出版日期2010-2