Lamina Propria T Cell Subsets in the Small and Large Intestine of Euthymic and Athymic Mice

Over the past decade it has become clear that probiotic and commensal interactions with mucosal dendritic cells in the lamina propria or epithelial cells lining the mucosa can modulate specific functions of the mucosal immune system. Innate pattern-recognition receptors such as TLRs, NLRs and CLRs play a crucial role in the host recognition of probiotics and other microorganism. Signalling via these receptors directly influences the chemokine and cytokine response of dendritic cells as well as the crosstalk between the epithelium and the immune cells in the lamina propria. This can influence the population of effector and regulatory T cell subsets in the mucosa. Immune assays with probiotics have shown that the in vitro immune response is both species and strain-specific. Such assays may be useful for the selection of probiotic strains that have beneficial effects on the regulation of intestinal inflammation but more comparative studies are needed to confirm recent findings. A better understanding of the molecular mechanisms of probiotics, the effect of dose, and frequency of administration on microbial sampling by mucosal APC will also help to clarify the value of immune assays as selection criteria for probiotics.

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Histopathological Features of Inflammatory Bowel Disease are Associated With Different CD4+ T Cell Subsets in Colonic Mucosal Lamina Propria

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjy116 ◽

2018 ◽

Cited By ~ 6

Author(s):

Xianyong Gui ◽

Ji Li ◽

Aito Ueno ◽

Marietta Iacucci ◽

Jiaming Qian ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

T Cell ◽

Lamina Propria ◽

Bowel Disease ◽

T Cell Subsets ◽

Cd4 T Cell ◽

Histopathological Features ◽

Inflammatory Bowel ◽

Mucosal Lamina Propria

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Effects of the oral administration of the products derived from milk fermentation by kefir microflora on immune stimulation

Journal of Dairy Research ◽

10.1017/s002202990600197x ◽

2006 ◽

Vol 73 (4) ◽

pp. 472-479 ◽

Cited By ~ 40

Author(s):

Gabriel Vinderola ◽

Gabriela Perdigón ◽

Jairo Duarte ◽

Edward Farnworth ◽

Chantal Matar

Keyword(s):

Small Intestine ◽

Blood Serum ◽

Lamina Propria ◽

Large Intestine ◽

Milk Fermentation ◽

Gut Mucosa ◽

Iga Production ◽

Fermented Dairy ◽

Small And Large Intestine

Nutritional status has a major impact on the immune system. Probiotic effects ascribed to fermented dairy products arise not only from whole microorganisms but also from metabolites (peptides, exopolysaccharides) produced during the fermentation. We recently demonstrated the immunomodulating capacity of kefir in a murine model. We now aimed at studying the immunomodulating capacity in vivo of the products derived from milk fermentation by kefir microflora (PMFKM) on the gut. BALB/c mice received the PMFKM for 2, 5 or 7 consecutive days. IgA+ and IgG+ cells were determined on histological slices of the small and large intestine. IL-4, IL-6, IL-10, IL-12, IFNγ and TNFα were determined in the gut, intestinal fluid and blood serum. IL-6 was also determined in the supernatant of a primary culture of small intestine epithelial cells challenged with PMFKM. PMFKM up-regulated IL-6 secretion, necessary for B-cell terminal differentiation to IgA secreting cells in the gut lamina propria. There was an increase in the number of IgA+ cells in the small and large intestine. The increase in the number of IgA+ cells was accompanied by an increase in the number of IL-4+, IL-10+ and IL-6+ cells in the small intestine. Effects of PMFKM in the large intestine were less widely apparent than the ones observed at the small intestine lamina propria. All cytokines that increased in the small intestine lamina propria, also did so in blood serum, reflecting here the immunostimulation achieved in the gut mucosa. We observed that the PMFKM induced a mucosal response and it was able to up and down regulate it for protective immunity, maintaining the intestinal homeostasis, enhancing the IgA production at both the small and large intestine level. The opportunity exists then to manipulate the constituents of the lumen of the intestine through dietary means, thereby enhancing the health status of the host.

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Rapid Acquisition of Tissue-specific Homing Phenotypes by CD4+ T Cells Activated in Cutaneous or Mucosal Lymphoid Tissues

Journal of Experimental Medicine ◽

10.1084/jem.20011502 ◽

2002 ◽

Vol 195 (1) ◽

pp. 135-141 ◽

Cited By ~ 374

Author(s):

Daniel J. Campbell ◽

Eugene C. Butcher

Keyword(s):

T Cells ◽

T Cell ◽

Lymph Nodes ◽

Lamina Propria ◽

Memory T Cells ◽

Lymphoid Organs ◽

T Cell Subsets ◽

Effector Memory ◽

Intestinal Lamina Propria ◽

Tissue Specific

Effector and memory T cells can be subdivided based on their ability to traffic through peripheral tissues such as inflamed skin and intestinal lamina propria, a property controlled by expression of ‘tissue-specific’ adhesion and chemoattractant receptors. However, little is known about the development of these selectively homing T cell subsets, and it is unclear whether activation in cutaneous versus intestinal lymphoid organs directly results in effector/memory T cells that differentially express adhesion and chemoattracant receptors targeting them to the corresponding nonlymphoid site. We define two murine CD4+ effector/memory T cell subsets that preferentially localize in cutaneous or intestinal lymphoid organs by their reciprocal expression of the adhesion molecules P-selectin ligand (P-lig) and α4β7, respectively. We show that within 2 d of systemic immunization CD4+ T cells activated in cutaneous lymph nodes upregulate P-lig, and downregulate α4β7, while those responding to antigen in intestinal lymph nodes selectively express high levels of α4β7 and acquire responsiveness to the intestinal chemokine thymus-expressed chemokine (TECK). Thus, during an immune response, local microenvironments within cutaneous and intestinal secondary lymphoid organs differentially direct T cell expression of these adhesion and chemoattractant receptors, targeting the resulting effector T cells to the inflamed skin or intestinal lamina propria.

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Different Sensitivity of Lamina Propria T-Cell Subsets to Nitric Oxide-Induced Apoptosis Explains Immunomodulatory Activity of a Nitric Oxide--Releasing Derivative of Mesalamine in Rodent Colitis

Gastroenterology ◽

10.1053/j.gastro.2005.01.051 ◽

2005 ◽

Vol 128 (5) ◽

pp. 1243-1257 ◽

Cited By ~ 16

Author(s):

Luca Santucci ◽

John Wallace ◽

Andrea Mencarelli ◽

Silvana Farneti ◽

Antonio Morelli ◽

...

Keyword(s):

Nitric Oxide ◽

T Cell ◽

Lamina Propria ◽

T Cell Subsets ◽

Immunomodulatory Activity ◽

Induced Apoptosis ◽

Nitric Oxide Releasing

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Immune checkpoint inhibitor-associated celiac disease

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-000958 ◽

2020 ◽

Vol 8 (1) ◽

pp. e000958 ◽

Cited By ~ 2

Author(s):

Yousef Badran ◽

Angela Shih ◽

Donna Leet ◽

Meghan J Mooradian ◽

Alexandra Coromilas ◽

...

Keyword(s):

T Cells ◽

Celiac Disease ◽

T Cell ◽

Lamina Propria ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitor ◽

Checkpoint Inhibitor ◽

Γδ T Cells ◽

T Cell Subsets ◽

Programmed Death

BackgroundRare cases of immune checkpoint inhibitor (ICI)-associated celiac disease (ICI-CeD) have been reported, suggesting that disruption of tolerance mechanisms by ICIs can unmask celiac disease (CeD). This study aims to characterize the clinicopathological and immunophenotypic features of ICI-CeD in comparison to ICI-associated duodenitis (ICI-Duo) and usual CeD.MethodsA medical and pathological records search between 2015 and 2019 identified eight cases of ICI-CeD, confirmed by tTG-IgA. Nine cases of ICI-Duo, 28 cases of moderate CeD, as well as 5 normal controls were used as comparison groups. Clinical information was collected from the electronic medical records. Immunohistochemistry for CD3, CD8, T-cell receptor gamma/delta (γδ), programmed death ligand 1 (PD-L1), and programmed death 1 (PD-1) were performed, with quantification of intraepithelial lymphocyte (IEL) subsets in three well-oriented villi. CD68, PD-L1, and PD-1 were assessed as a percentage of lamina propria surface area infiltrated by positive cells. Statistical significance was calculated by the Student’s t-test and Fisher’s exact test.ResultsThe eight patients with ICI-CeD (F:M=1:3) and nine patients with ICI-Duo (F:M=5:4) presented similarly with diarrhea (13/17) and abdominal pain (11/17) after a median of 1.6 months on ICI therapy. In patients with ICI-CeD, tTG-IgA ranged from 104 to >300 IU/mL. Histological findings in ICI-CeD and ICI-Duo were similar and included expansion of the lamina propria, active neutrophilic duodenitis, variably increased IELs, and villous blunting. Immunohistochemistry showed that the average number of IELs per 100 enterocytes is comparable between ICI-CeD and ICI-Duo, with increased CD3+ CD8+ T cells compared with normal duodenum but decreased γδ T cells compared with CeD. Average PD-L1 percentage was 9% in ICI-CeD and 18% in ICI-Duo, in comparison to <1% in CeD and normal duodenum; average PD-1 percentage was very low to absent in all cases (<3%). On follow-up, five patients with ICI-CeD improved on a gluten-free diet (GFD) as the sole therapeutic intervention (with down-trending tTG-IgA) while the other three required immunosuppression. All patients who developed ICI-Duo received immunosuppression with variable improvement in symptoms.ConclusionsICI-CeD resembles ICI-Duo clinically and histologically but shares the serological features and response to gluten withdrawal with classic CeD. Immunophenotyping of IELs in ICI-CeD and ICI-Duo also shows similar CD3, CD8, γδ T cell subsets, and PD-L1 populations, all of which differed quantitatively from usual CeD. We conclude that ICI-CeD is biologically similar to ICI-Duo and is likely a variant of ICI-Duo, but treatment strategies differ, with ICI-CeD often improving with GFD alone, whereas ICI-Duo requires systemic immunosuppression.

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P095 PD-1 expressing T cells in patients with different types of colitis

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.224 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S182-S183

Author(s):

B Roosenboom ◽

C Horjus Talabur Horje ◽

C Smids ◽

J W Leeuwis ◽

E Van Koolwijk ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Lamina Propria ◽

Cell Activity ◽

T Cell Subsets ◽

Healthy Controls ◽

Infectious Colitis ◽

Biopsy Specimens ◽

Different Types ◽

Lymphocyte Activity

Abstract Background Immunotherapy-related colitis is a frequent adverse event in patients with malignancies, treated with inhibitors targeting programmed death-1 (PD-1). This treatment leads to enhancement of lymphocyte activity, thereby generating antitumor T-cell activity. The role of PD-1+ T cells in the pathophysiology of different types of colitis is unclear. Therefore, we aimed to study the presence of PD-1+ T cells in inflammatory bowel disease (IBD), infectious colitis and healthy controls compared with anti-PD-1-related colitis. Methods We performed a prospective cohort study. Newly diagnosed patients with ulcerative colitis (UC, n = 51), Crohn’s disease (CD, n = 29), infectious colitis (n = 4), anti-PD-1-related colitis (n = 5) and healthy controls (n = 6) were included. Baseline colonic biopsy specimens were collected for immunohistochemistry identifying PD-1+ and PD-L1+ lymphocytes in the epithelium and lamina propria separately and for immunophenotyping by flow cytometry identifying PD-1+ T-cell subsets. Results Using immunohistochemistry, PD-1 was not present on lymphocytes in the epithelium of patients with any type of colitis, nor in healthy controls. Of all lymphocytes in the lamina propria, % PD-1 expression was 40% in UC, 5% in infectious colitis, 3% in anti-PD-1-related colitis and 0% in healthy controls. PD-L1 was expressed on lymphocytes in the epithelium and lamina propria of UC patients (12.5% and 40%) and in infectious colitis (1% and 30%), whereas in anti-PD-1-related colitis (0% and 15%) and healthy controls (0% and 15%) no PD-L1+ lymphocytes were demonstrated in the epithelium. Flowcytometry showed higher percentages of PD-1+ T cells in biopsy specimens of UC patients (25.2% (IQR 17.9–35.6)) compared with all other groups; CD patients (13.5% (5.0–25.3), p = 0.001), infectious colitis (9.8% (4.7–17.4), p = 0.005), anti-PD-1-related colitis (1.5% (1.1–2.1), p = 0.001) and healthy controls (14.3% (4.9–28.2), p = 0.08). In IBD and infectious colitis, the majority of PD-1+ T cells were CD4+ (84.8% (76.5–90.5), while in anti-PD-1-related colitis the majority of PD-1+ T cells were CD8+ (76.2% (68.5–82.1)). PD-1+ T cells in all patient groups were mainly effector T cells (CD45Ro+). Conclusion In patients with different types of colitis and in healthy controls, PD-1 was only expressed on T cells in the lamina propria and not in the epithelium. The percentage of PD-1+ T cells was significantly higher in patients with UC compared with patients with CD or infectious colitis and healthy controls. As expected PD-1+ T cells were nearly absent in patients with anti-PD-1-related colitis.

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