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Distribution of mucosal PD-1 expressing T cells in patients with colitis of different etiologies
Britt Roosenboom1, Carmen S Horjus Talabur Horje1, Carolijn Smids1
1Department of Gastroenterology and Hepatology, Rijnstate Crohn & Colitis Center, Rijnstate Hospital, Arnhem, The Netherlands.
Background:
Immunotherapy, targeting programmed death-1 (PD-1) enhances antitumor T-cell activity in patients with malignancies. Blocking PD-1 or its ligand may lead to fulminant colitis as serious adverse event in these patients. Since little is known of the presence and role of PD-1+T cells in colitis of different etiologies, we determined PD-1+T cells in mucosal specimens of patients with inflammatory bowel disease, infectious colitis (InfC), immunotherapy-related colitis (ImC) and healthy controls (HC).
Methods:
Newly diagnosed patients with ulcerative colitis (UC, n = 73), Crohn's disease (CD, n = 50), InfC (n = 5), ImC (n = 8) and HC (n = 8) were included. Baseline inflamed colonic biopsies were studied with immunohistochemistry and flowcytometry.
Results:
Using immunohistochemistry, PD-1 was not present on lymphocytes in the epithelium of all patients, nor in HC. The percentage PD-1+ of all lymphocytes in the lamina propria was 40% in UC, 5% in InfC, 3% in ImC and 0% in HC. Flowcytometry showed significant higher percentages of PD-1+T cells in inflamed biopsy specimens of UC patients (22%) compared to all other groups: CD patients (13%), InfC (12%), ImC (5%) and HC (6%).
Conclusion:
There are relevant differences in distribution and frequencies of mucosal PD-1+ T-cell subsets in patients with UC, CD, InfC and ImC, supporting the hypothesis that these types of colitis are driven by different immunological pathways. The increased numbers of PD-1+ and PD-L1+ lymphocytes in the colonic mucosa of UC patients suggest that the PD-1/PD-L1 pathway might be more activated in UC than in CD.
Insights
Programmed death-1 (PD-1) T cells are elevated in ulcerative colitis (UC) mucosal tissues, unlike other colitis types. This suggests distinct immune pathways drive UC, potentially involving the PD-1/PD-L1 pathway.
Area of Science:
- Immunology
- Gastroenterology
- Oncology
Background:
- Immunotherapy targeting programmed death-1 (PD-1) enhances anti-tumor T-cell activity but can cause severe colitis.
- The role of PD-1 positive (PD-1+) T cells in various colitis etiologies is not well understood.
- This study investigates PD-1+ T cells in inflammatory bowel disease (IBD), infectious colitis (InfC), immunotherapy-related colitis (ImC), and healthy controls (HC).
Purpose of the Study:
- To determine the presence and frequency of PD-1+ T cells in the colonic mucosa of patients with different types of colitis.
- To compare PD-1+ T cell distribution across ulcerative colitis (UC), Crohn's disease (CD), InfC, ImC, and HC groups.
- To explore the potential role of the PD-1/PD-L1 pathway in the immunopathogenesis of UC.
Main Methods:
- Inclusion of newly diagnosed patients with UC (n=73), CD (n=50), InfC (n=5), ImC (n=8), and HC (n=8).
- Analysis of baseline inflamed colonic biopsies using immunohistochemistry and flow cytometry.
- Quantification of PD-1+ lymphocytes within the colonic epithelium and lamina propria.
Main Results:
- PD-1 was not detected on lymphocytes in the colonic epithelium across all groups.
- The percentage of PD-1+ lymphocytes in the lamina propria was highest in UC (40%), followed by InfC (5%), ImC (3%), and HC (0%).
- Flow cytometry revealed significantly higher percentages of PD-1+ T cells in inflamed UC biopsies (22%) compared to CD (13%), InfC (12%), ImC (5%), and HC (6%).
Conclusions:
- Significant differences exist in the distribution and frequency of mucosal PD-1+ T-cell subsets among UC, CD, InfC, and ImC patients.
- These findings support the hypothesis that distinct immunological pathways drive different types of colitis.
- Elevated PD-1+ and PD-L1+ lymphocytes in UC mucosa suggest increased PD-1/PD-L1 pathway activation in UC compared to CD.
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