P100 CD161 levels are reduced in all subpopulations of T-cell colonic mucosal lymphocytes in inflammatory bowel disease

E. Tristan, A. Carrasco, A. Martín-Cardona, Y. Zabana, M. Aceituno, A. Raga, X. Andújar, B. Arau, P. Ruiz-Ramírez, L. Ruiz-Campos, F. Fernández-Bañares, M. Esteve

Gastroenterology Department, Hospital Universitari Mútua Terrassa, Universitat de Barcelona, Terrassa. Centro de Investigación Biomédica en red de enfermedades hepáticas y digestivas CIBERehd, Gastroenterology Department, Terrassa, Spain

Background

CD161 is a type C lectin expressed in NKs cells and peripheral T cells (TCRγδ and αβ, NKTs), enriched in intestinal populations. Its expression can be modulated by infections and inflammation. MAIT cells are a subset of innate antimicrobial T-cells abundant in the mucosa but their role in immunological regulation is still unknown.

Methods

Aim:

To measure CD161 levels in subtypes of T-lymphocytes of intestinal mucosa: CD4+, CD8+, double positive (DP,CD4+CD8+), double negative (DN,CD4CD8), MAIT cells (CD161+TCRVα7.2+) and intraepithelial cells (CD103+)

Results

Twenty-six patients with active inflammatory bowel disease (IBD) without immunosuppressive treatment (n = 9 Crohn’s disease -CD- colon, 9 CD ileum, n = 8 ulcerative colitis -UC- and 10 healthy controls (paired biopsies of ileum, right and left colon) were included. Lymphocyte subpopulations were analysed with LSRFortessa cytometer. Non-parametric Kruskal–Wallis test was applied. Results are expressed as % of median (25–75%IQI).

Conclusion

In healthy mucosa, we did not find differences related to location in any of CD161 subpopulations except for increase of CD3+CD161+CD103+ and decrease of CD3+CD161+CD103 in left colon compared with right colon and ileum. Regarding MAIT cells, a progressive decrease was observed in distal parts of intestine for CD3+MAIT+CD103+ while CD3+MAIT+CD103 subpopulation has a specular behaviour; CD3+CD8+MAIT+ was increased in ileum compared with colon (Table 1).

Healthy intestineIleumRight colonLeft colonp-value
CD3+CD161+CD10343.2 (33.3-63.0)41.5 (26.4-55.8)26.0 (18.7-35.2)0.034
CD3+CD161+CD103+56.8 (42.2-66.6)58.4 (44.1-73.5)73.9 (64.7-81.1)0.029
CD3+MAIT+CD103+57.1 (41.2-63.5)42.7 (24.7-52.2)32.4 (22.4-43.7)0.042
CD3+MAIT+CD10345.6 (36.5-58.7)57.2 (47.7-75.2)67.5 (57.8-77.5)0.037
CD3+CD8+MAIT+3.2 (2.2-5.4)1.7 (1.2-2.5)1.8 (1.5-2.2)0.019

In ileal CD vs. healthy ileal mucosa, no differences were observed regarding CD3+CD161+ and CD3+MAIT+. A reduction of CD3+CD161+ was observed in colonic IBD compared with controls due to a reduction of CD3+CD4+CD161+, CD3+CD8+CD161+ and CD3+DN_CD161+ (Table 2).

Left colonUCCDHealthyp-value
CD3_CD16135.9 (28.1-42.7)39.8 (33.0-55.1)61.2 (57.7-67.5)0.004
CD3+CD4+CD161+39.1 (37.2-56.0)47.0 (38.3-62.5)71.8 (68.3-77.0)0.001
CD3+CD8+CD161+14.0 (12.3-25.3)21.5 (15.6-45.7)49.1 (33.3-56.9)0.013
CD3+DN_CD161+16.0 (12.2-24.3)18.4 (14.3-49.3)45.6 (23.4-57.8)0.008

There is a regional specialisation for the subset CD103+ of both CD161+CD103+ and MAIT_CD103+ cells in healthy intestine. CD3+CD161+ T cells are reduced in IBD colonic inflammation and could serve as a marker of active IBD but not to sort between CD and UC.