Table 1.
The contribution of CD8+ T cells in IBD.
| Ref. | Key findings | Disease/disease status | CD8+ T cell origin | Experimental Settings |
|---|---|---|---|---|
| Gasparetto et al., 2021 (29) | Transcriptional signature and DNA methylation profiles of circulating CD8+ T cells from pediatric patients with active IBD does not correlate to clinical outcome | Pediatric active CD and UC | PBMCs | Genome transcript analysis of magnetic-sorted CD8+ |
| Jaeger et al., 2021 (30) | Intraepithelial and lamina propria compartments harbor similar CD8+ T cell subsets. Circulating and tissue resident CD8+ T subsets were found in the intraepithelial compartment. CD8+ T cells were increased in non-inflamed LP of CD, whereas CD8+ T cells were decreased in the intraepithelium at sites of inflammation. KLRG1+ CD8+ T frequencies showed no difference between patients and CD patients. | Severe CD | Inflamed and non-inflamed terminal ileum biopsies | CyTOF and scRNA-seq on CD45+ IEL and LP cells. Cluster analysis on CD8+ cells |
| Boland et al., 2020 (19) | Single cell atlas of colonic CD8+ T cells from UC patients revealed highly heterogeneic populations. CD8+ Trm might be involved in the development of UC. | Active UC | PBMCs and rectal biopsies | scRNA-seq on CD45+ cells. Cluster analysis on CD8+ cells |
| Bottois et al., 2020 (20) | High numbers of CD103+ CD8+ Trm were found in the mucosa of CD patients and controls, but those from patients had a more prominent Th17 profile. KLRG1+ CD8+ Trm cells were increased in inflammatory conditions. In Crohn´s disease patients the CD103+ CD8+ T cells might alert the effector KLRG1+ CD8+ T subset. | Active CD | PBMC as well as inflamed and non-inflamed ileum biopsies | CD5+ magnetic and Aria sorted |
| Bruckner et al., 2020 (31) | Pro-inflammatory TNFα+ CD8+ T cells play a role on the development of fistulas in CD patients. | CD with fistula | Biopsies from acute inflamed fistulas | FACS on CD8+ cells |
| Corridoni et al., 2020 (21) | Single cell atlas of colonic CD8+ T cells from biopsies of UC patients. Informative platform for future functional studies. | Active UC | Inflamed colonic biopsies | scRNA-seq on CD3+ CD8+ cells |
| Libera et al., 2020 (32) | Mucosal-derived CD39+ CD8+ T cell frequency was decreased in IBD patients compared to healthy controls | Active CD and UC | PBMCs and colonic biopsies | FC analysis on CD39+ CD8+ cells |
| Noble et al., 2020 (33) | Circulating CD8+ memory T cells from HDs respond to intestinal bacteria derived antigens. Reduced numbers of mucosal CD8+ Trm were observed in IBD patients compared to controls. | CD and UC | Non-inflamed colonic biopsies and PBMC | FC analysis on CD103+ Runx3+ CD8+ |
| Huang et al., 2019 (34) | Colonic GZMK+ (granzyme K) CD8+ Tem cells were clonally expanded in a pediatric IBD cohort with active disease. Furthermore, colonic ITGAE (CD103) CD8+ Trm and ENTPD1 (CD39) CD8+ Trm cells were decreased in pediatric IBD compared to controls. | Pediatric active CD and UC | Colonic biopsies | scRNA-seq on CD45+ cells. Cluster analysis on CD8+ cells |
| Rabe et al., 2019 (18) | Pediatric ulcerative colitis patients had higher levels of activated HLA.DR+ β1-integrin+ CD8+ T cells in the periphery and that correlated positively to systemic and mucosal inflammation biomarkers. Pediatric Crohn´s disease patients showed equal levels of activated HLA.DR+ β1-integrin+ CD8+ T cells to controls, but an increase on the CD23+ B cell population. | Newly diagnosed pediatric CD and UC | Blood | FC analysis on CD8+ |
| Roosenboom et al., 2019 (35) | Decreased percentage of CD103+ CD8+ T cells in the inflamed ileum and colon of IBD patients compared to controls. CD103+ CD8+ T cell frequencies were comparable between IBD patients in remission and controls. | Active CD and UC (including follow-up) | Biopsies from inflamed colon and ileum | FC analysis on CD103+ CD8+ |
| Smillie et al., 2019 (36) | Single cell atlas of colonic biopsies of UC patients revealed Tc17 subset as expanded, and major source of IL17, in inflamed tissue. | Active UC | Inflamed colonic biopsies | scRNA-seq on all cells. Cluster analysis on CD8+ cells |
| Zundler et al., 2019 (37) | Lamina propria CD103+ CD69+ CD8+ Trm cells were increased in inflamed mucosa of IBD patients compared to controls. | Active CD and UC | Colonic biopsies | FC analysis on CD103+ CD69+ CD8+ |
| Smids et al., 2018 (38) | CD103+ CD8+ Trm cells were decreased in inflamed tissue of IBD compared to non-inflamed biopsies and controls. Furthermore, CD8+ Tcm were increased in inflamed intestine biopsies of UC patients with active disease, whereas CD8+ Tem frequency was decreased compared to controls. | Active CD and UC | Biopsies of inflamed intestine and of follow-up endoscopies | FC analysis on CD8+ |
| Boschetti et al., 2016 (39) | Circulating and mucosal GrB+ perforin+ CTLs were abundant in CD patients with recurrent disease, compared to endoscopic remission and controls. | Recurrent CD | PBMC and curative ileum biopsies | FC analysis on CD8+ |
| Tom et al., 2016 (40) | The frequency of lamina propria CD8+ T regs was higher in IBD patients compared to controls. Lamina propria Tc17 prevalence was higher in UC patients compared to CD patients and controls. Circulating CD8+ T regs and Tc17 were increased in IBD patients compared to controls. | Active CD and UC | PBMC and inflamed mucosa biosies (LPMC) | FC analysis on CD8+ |
| Funderburg et al., 2013 (16) | Activated IFNγ+ CD8+ cells were increased in the peripheral blood of IBD patients, and correlate to higher levels of inflammation markers in serum. | Active CD and UC | PBMCs | FC analysis on CD8+ |
| Lee et al., 2011 (5) | Two distinctive CD8+ T cell expression signatures can be recognized in adult patients with active IBD, one that correlates to a mild outcome, and another one correlating to a severe one. CD8+ T cells might disrupt epithelial barrier playing an earlier role in the development of the disease. | Active CD and UC | PBMCs | CD8+ magnetic sorted |
| Brimnes et al., 2005 (41) | Regulatory activity of CD8+ T cells from lamina propria of healthy gut was observed in vitro, whereas CD8+ T cells from lamina propria of IBD patients showed no regulatory activity | CD and UC | LPMCs from colon | FACS on CD8+ |
CD8+ T cell subsets contribute to IBD in a different manner, some pools are pro-inflammatory whereas other are anti-inflammatory. The source where CD8 cells were obtained from might reflect different phenotypes, hence different functions of the cells. CD, Crohn’s disease; CyTOF, cytometry by time of flight; ENTPD1, ectonucleoside triphosphate diphosphohydrolase-1 (CD39-encoding gene); HDs, healthy donors; IEL, intraepithelial lymphocyte; ITGAE, integrin alpha E (CD103-encoding gene); FACS, fluorescence activated cell sorting; FC, flow cytometry; GrB, granzyme B; GZMK, granzyme K-encoding gene; LP, Lamina propria; LPMC, Lamina propria mononuclear cells; PBMCs, peripheral blood mononuclear cells; scRNA-seq, single cell RNA sequencing; Trm, resident memory T cells; UC, ulcerative colitis.