Cytotoxic T Cells in H. pylori-Related Gastric Autoimmunity and Gastric Lymphoma

Helicobacter pylori infection is the major cause of gastroduodenal pathologies, but only a minority of infected patients develop gastric B-cell lymphoma, gastric autoimmunity, or other life threatening diseases, as gastric cancer or peptic ulcer. The type of host immune response against H. pylori, particularly the cytolytic effector functions of T cells, is crucial for the outcome of the infection. T cells are potentially able to kill a target via different mechanisms, such as perforins or Fas-Fas ligand interaction. In H. pylori-infected patients with gastric autoimmunity cytolytic T cells, that cross-recognize different epitopes of H. pylori proteins and H+K+-ATPase autoantigen, infiltrate the gastric mucosa and lead to gastric atrophy via long-lasting activation of Fas ligand-mediated appotosis and perforin-induced cytotoxicity. On the other hand, gastric T cells from MALT lymphoma exhibit defective perforin- and Fas-Fas ligand-mediated killing of B cells, with consequent abnormal help for B-cell proliferation, suggesting that deregulated and exhaustive H. pylori-induced T cell-dependent B-cell activation can support both the onset and the promotion of low-grade B-cell lymphoma

T Cells and Adoptive Immunotherapy: Recent Developments and Future Prospects in Gastrointestinal Oncology

Gastrointestinal oncology is one of the foremost causes of death: the gastric cancer accounts for 10.4% of cancer deaths worldwide, the pancreatic cancer for 6%, and finally, the colorectal cancer for 9% of all cancer-related deaths. For all these gastrointestinal cancers, surgical tumor resection remains the primary curative treatment, but the overall 5-year survival rate remains poor, ranging between 20–25%; the addition of combined modality strategies (pre- or postoperative chemoradiotherapy or perioperative chemotherapy) results in 5-year survival rates of only 30–35%. Therefore, many investigators believe that the potential for making significant progress lies on understanding and exploiting the molecular biology of gastrointestinal tumors to investigate new therapeutic strategies such as specific immunotherapy. In this paper we will focus on recent knowledge concerning the role of T cells and the use of T adoptive immunotherapy in the treatment of gastrointestinal cancers

Stimulation of TH1 response by Helicobacter pylori neutrophil activating protein decreases the protective role of IgE and eosinophils in experimental trichinellosis

Th2 responses seem to play an important role in defence against Trichinella spiralis (Ts). The Neutrophil Activating Protein of Helicobacter pylori (HP-NAP), that induces IL-12, and IL-23 expression and shifts to Th1 allergen-specific Th2 cells in vitro was used as an anti-Th2 agent in BALB/c mice infected with T. spiralis. The muscle larvae (ML) burden was lower (p < 0.02) in untreated infected animals than those infected treated with HP-NAP. In both groups there was an inverse relationship between ML burden of each animal and total IgE level (controls: r -0.617,p = 0.0013 and HP-NAP-treated: r -0.678,p = 0.0001) or eosinophil count, evaluated in the same mouse on day 42 (r -0.390,p = 0.0592 and r -0.803,p = 0.0001, respectively). Inflammatory response around the nurse cell-parasite complex was significantly higher in HP-NAP-treated infected animals than in those untreated infected, on the contrary the number of eosinophils, counted around each complex was significantly lower in the first animal group. This study provides evidence of a powerful anti-Th2 activity in vivo by HP-NAP and for the partial protective effect of Th2 responses in T. spiralis infection

Usefulness of (13)C-urea breath test in the diagnosis of gastric helicobacter pylori infection

Helicobacter pylori chronically infects half of the human population and is associated with gastritis, peptic ulcer and gastric cancer. C-13-urea breath test (UBT) is the main in vivo tool for the diagnosis of H. pylori infection. In this study, the safety and the accuracy of UBT were evaluated.A group of 492 dyspeptic patients was studied by UBT, the results were expressed as the difference over baseline at 30 min (DOB30). All patients were evaluated for systemic, gastrointestinal or allergic-type adverse reactions after ingestion of 75 mg C-13-urea and citric acid in aqueous solution, The first 256 patients enrolled also underwent endoscopy and gastric biopsy. Patients positive on histology were considered infected.UBT was well tolerated and none of the 492 patients had any systemic or allergic-type adverse reaction. Among the 256 patients studied with histology, 116 were H. pylori positive on biopsies. Using 4 %o as cut-off value for DOB30, 115 out of the 256 patients were positive on UBT, with only 2 false positive and 3 false negative, With this threshold, the sensitivity, specificity, and accuracy of the UBT were 97.4 %, 98.5 %, and 98.0 %, respectively.C-13-UBT has proven to be a safe and simple, yet accurate, test for the non-invasive diagnosis and monitoring of H. pylori infection

Interleukin 17 producing T cell responses in human chronic trichinellosis-insight from a case study

Introduction: We studied the cellular immune response in a patient infected since 10 months (along with other 51 people) during a trichinellosis outbreak caused by Trichinella spp. Methods: A 46 years old female resulted serologically positive for trichinellosis. We isolated peripheral blood mononuclear cells (PBMCs) and incubated them with excretory/secretory antigens (ESA) of Trichinella spiralis (T1) or Trichinella pseudospiralis (T4) to produce antigen specific T cell lines and clones, analysed for the phenotype (T helper or cytotoxic cells), for their T4 or T1 antigens specificity and for their cytokine profile (IFNγ, IL-17A, IL-4) by flow cytometry, thymidine incorporation assay and ELISpot. Results: The test performed using ESA from T1 or T4 has identified the species responsible for infection as T. pseudospiralis since the proliferative responses (evaluated by CFSE, Carboxyfluorescein succinimidyl ester, FACS analysis) was higher for T4 (72,8%) than T1 (23.6 %) antigen. The cell lines produced significant levels of IFNγ, IL-4 and IL-17A after stimulation. From the T cell line obtained in response to T1 ESA, as regards CD4 + cells, 12 % Th2, 22.8 % Th1, 6.6 % Th17, 6 % Th0, 2.2 % Th1/Th17 and 0.7 % Th2/Th17, were obtained. From the T1-specific TCL we generated 15 clones. From the TCL specific for T4 ESA, as regards CD4+, 15.2 % Th2, 27.1 % Th1, 3 % Th17, 10.3 %Th0, 1.9 % Th1/Th17 and 1 % Th2/ Th17 were obtained. From such TCL 4 clones were isolated, 1Th2, 1 Th1, 1 Th17, 1 Th1/Th17 and no Th0 nor Th2/Th17. Conclusions: By cellular immunology techniques the species responsible of the infection resulted T. pseudospiralis, confirming the results previously obtained by serology. For the first time it was revealed in a human chronic infection the presence of Th17 cells

Systemic lupus erythematosus: immunopathogenesis and novel therapeutic targets

Systemic lupus erythematosus (SLE) is the prototype of autoimmune diseases with multiorgan involvement. SLE presents many genetic and epigenetic associations and the pathogenesis is characterized by a complex network of alterations affecting both adaptative and innate immunity. The disclosure of novel mechanisms of SLE pathogenesis suggested new therapeutic targets, based on interference with the cytokine pathways or on depletion of the immune cells

T Cells in Gastric Cancer: Friends or Foes

Gastric cancer is the second cause of cancer-related deaths worldwide. Helicobacter pylori is the major risk factor for gastric cancer. As for any type of cancer, T cells are crucial for recognition and elimination of gastric tumor cells. Unfortunately T cells, instead of protecting from the onset of cancer, can contribute to oncogenesis. Herein we review the different types, “friend or foe”, of T-cell response in gastric cancer