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

Abstract

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.