Submit a Letter to the Editor for:
Abdelaziz Amrani, Joan Verdaguer, Brad Anderson, Toshihiro Utsugi, Sonny Bou, Pere Santamaria
J Clin Invest. 1999;
103(8):1201
doi:10.1172/JCI6266
Abstract |
Full text
|
PDF
A
utoimmune diabetes in nonobese diabetic (NOD) mice results from destruction of pancreatic β cells by T lymphocytes. It is believed that CD8+ cytotoxic T lymphocytes (CTLs) effect the initial β-cell insult in diabetes, but the mechanisms remain unclear. Studies of NOD.lpr mice have suggested that disease initiation is a Fas-dependent process, yet perforin-deficient NOD mice rarely develop diabetes despite expressing Fas. Here, we have investigated the role of perforin and Fas in the ability of β cell–reactive CD8+ T cells bearing a T-cell receptor (8.3-TCR) that is representative of TCRs used by CD8+ CTLs propagated from the earliest insulitic lesions of NOD mice, and that targets an immunodominant peptide/H-2Kd complex on β cells, to effect β-cell damage in vitro and in vivo. In vitro, 8.3-CTLs killed antigenic peptide–pulsed non–β-cell targets via both perforin and Fas, but they killed NOD β cells via Fas exclusively. Perforin-deficient 8.3-TCR–transgenic NOD mice expressing an oligoclonal or monoclonal T-cell repertoire developed diabetes even more frequently than their perforin-competent littermates. These results demonstrate that diabetogenic CD8+ CTLs representative of CTLs putatively involved in the initiation of autoimmune diabetes kill β cells in a Fas-dependent and perforin-independent manner.
Guidelines:
The Editorial Board will only consider letters that we deem relevant and of interest to our readers. We will not post data that have not been subjected to peer review, nor will we post letters that are essentially a reiteration of another letter. All accepted letters will be posted on our website within one week of acceptance. The Editors reserve the right to edit any letter for length, content, and clarity. Authors of all accepted letters will be asked to preview any changes. Authors will be notified by e-mail if their letters were not accepted. As this is a final decision, no appeals will be considered.
Specific requirements: All letters must be 400 words or fewer. You may enter the letter as plain text or HTML, if you wish. The author's name and e-mail address are required, and will be posted with the letter. All possible conflicts of interest must be noted, even if they are not posted. If you wish to include a figure (keep in mind that non-peer-reviewed data will not be posted), please contact the editor directly at editors@the-jci.org.
