Enrichment of Circulating and Mucosal Cytotoxic CD8+ T Cells Is Associated with Postoperative Endoscopic Recurrence in Patients with Crohn's Disease

Background and Aims: Evidence from mouse colitis models indicates that cytotoxic CD8(+) T cells [CTL] play a key role in the initiation of gut lesions. We investigated whether changes in CD8(+) CTL in blood or lamina propria [LP] of the neoterminal ileum were associated with postoperative endoscopic recurrence of Crohn's disease [CD]. Methods: A total of 37 CD patients with ileocolonic resection were endoscopically followed up at 6 and 12 months post-surgery. CD8(+) T cells were analysed by flow cytometry in blood and ileal LP. Results: Granzyme B- and perforin-producing CD8(+) T cells were significantly increased at 6 months in blood and in ileum LP in patients with endoscopic recurrence, as compared with those in remission. At a cutoff point of 45% of CD8(+) CTL, the overall accuracies of the frequency of blood granzyme B+ or perforin(+) CD8(+) T cells to identify patients with postoperative endoscopic recurrence were 77% and 83%, respectively. Interestingly, patients with endoscopic recurrence at 12 months were those showing the highest mucosal CD8(+) CTL frequency at 6 months, while still in remission. Conclusions: Enrichment of cytotoxic CD8(+) T cells in blood and ileal mucosa coincides with CD postoperative endoscopic recurrence. This underscores that CD8 CTL may play a pathophysiological role in the initiation of gut lesions during CD.