Hyperactivation and enhanced cytotoxicity of reduced CD8 gamma delta T cells in the intestine of patients with Crohn's disease correlates with disease activity.

Background And Aims: We aimed to investigate the immune characteristics of intestinal CD8 gamma delta T (CD8 γδ T) cells in Crohn's disease (CD) and their correlation with disease activity.

Methods: The study cohorts included 21 CD patients and 21 healthy individuals. CD8 γδ T cells were isolated from human ileal mucosa for detection by flow cytometry. The activation or inhibition status of cells was detected by detecting the expression of activation marker HLA-DR and the immunosuppressive molecule PD-1 on cells. The cytotoxicity of cells was assessed by detecting the expression of cytotoxic molecules (Perforin, Granzyme B, and TRAIL) in cells. Ratios of investigated cells were calculated as prediction factors by receiver operating characteristic curve (ROC) analysis.

Results: The study revealed a reduction in intestinal CD8 γδT cells among active CD patients, with a more pronounced reduction observed in moderately active patients compared to mildly active patients. Moreover, active CD patients exhibited heightened activation levels in their intestinal CD8 γδT cells, whereas the activation was comparatively weakened in moderately active patients compared with mildly active patients. Additionally, the cytotoxicity of intestinal CD8 γδT cells was enhanced solely in mildly active patients, while it was impaired in moderately active patients compared with mildly active patients. Furthermore, HLA-DR CD8 γδT cell ratio, CD8 γδT ratio, and CD8 γδT count were identified as indicators in the diagnosis of active CD. Meanwhile, the ratios of Granzyme B CD8 γδT cell and Perforin CD8 γδT cell were identified as indicators that distinguish mildly moderately active CD cases.

Conclusions: Intestinal CD8 γδT was reduced in active CD patients, but their activation and cytotoxicity were enhanced. However, with increased disease activity, intestinal CD8 γδ T cells became dysfunctional. CD-specific perturbations observed in various phenotypic markers in CD8 γδ T cells can be used as indicators to assist in diagnosing CD patients.