Intestinal Lymph Research Articles

PTH-268 The malignant colorectal polyp – how useful is the ACPGBI risk stratification score?

<h3>Introduction</h3> Colonic polyps containing a focus of invasive malignancy are increasing in frequency with the wider adoption of colonoscopic screening. Decision making as to the next course of action following endoscopic removal of a malignant polyp can be challenging. The ACPGBI position statement on malignant polyps outlines a scoring system to help predict the likelihood of lymph node metastasis and predicate surgical resection of the affected intestine and regional lymph nodes. The aim of this study was to analyse the benefit of this scoring system in predicting the presence of residual disease in patients with a malignant polyp. <h3>Method</h3> Colorectal MDT decision making and outcomes of a consecutive series of malignant polyps treated between 2008 and 2014 was studied. Each polyp was assigned an ACPGBI score retrospectively to assess how well this predicted the presence of residual disease. <h3>Results</h3> 70 patients (47 male) were identified as having a malignant polyp. Median follow-up was 27 months (range 0–58). Median age was 69 years (range 42–87). 36 (51%) polyps were detected during bowel cancer screening colonoscopy, 30 polyps were detected in symptomatic patients. 31 (45%) polyps were located in the rectum, 35 (51%) in the left colon and 3 (4%) in the right colon. 18 polyps were scored as low risk (ACPGBI score &lt;2, chance of residual disease &lt;5%). 15 patients were managed with endoscopic polypectomy only, all were recurrence-free during follow up. 3 patients underwent surgery, two after MDT recommendation and one as a result of perforation following polypectomy. None of these patients had residual disease in the specimen. 52 patients were deemed to have a moderate or high risk polyp (ACPGBI score 3 or more, &gt;10% risk residual disease). 2 patients were deemed unfit for surgery and 2 patients declined surgery. 48 patients underwent surgery: residual (lymph node) disease was found in 3 patients (ACPGBI Scores 4,4 &amp;5) and a further 1 patient (ACPGBI score 6), had a specimen clear of tumour but went on to develop metastatic disease giving an overall risk of residual disease of 8.3%. One patient is alive with metastatic disease and 3 patients have died post operatively, 1 (2.8%) of postoperative complications. The remaining patients are alive and recurrence-free. <h3>Conclusion</h3> Low-risk malignant polyps are readily identified using a composite score and do not require surgical resection of the affected colon or rectum. Criteria used to identify moderate risk polyps are not specific enough as most patients undergoing surgery do not harbour residual disease. Piecemeal removal of polyps makes accurate risk assessment difficult. Accumulation of data such as this will allow fine-tuning of criteria used to identify patients at greatest risk of residual cancer after endoscopic resection of a malignant polyp. <h3>Disclosure of interest</h3> None Declared.

Yersinia pseudotuberculosis infection in an adult Boer goat

This case report describes a Yersinia pseudotuberculosis infection in an adult, female single pet goat kept on a dairy cattle farm. The doe showed the habitus of a chronically ill...

English

Thirty sheep/lambs were brought for post mortem in Teaching Veterinary Clinical Complex, LUVAS and Central Sheep Breeding Farm, Hisar, which were investigated for gastrointestinal tract pathology in laboratory of Department of Veterinary Pathology. Mortality was maximum in sheep/lambs of age group 6 months to 1 year and higher in males than females. Gross pathological changes in gastro intestinal system noticed were congestion in abomasum, intestine, pancreas, liver and mesenteric lymph nodes. Histopathologically, there was congestion, desquamation of mucosal epithelium, submucosa in abomasum and small intestine including goblet cell hyperplasia. Congestion along with mild necrosis in pancreatic acini, liver parenchyma, peri portal area and mesenteric lymph node was observed along with haemorrhage in peri portal area and thrombosis of portal blood vessel in liver. Cloudy swelling, fatty changes, centrilobular necrosis in parenchyma and bile duct hyperplasia in liver was also reported.&nbsp; &nbsp; Key words: Gastro-intestinal, gross changes, histopathology, sheep. &nbsp

Sinomenine suppresses collagen-induced arthritis by reciprocal modulation of regulatory T cells and Th17 cells in gut-associated lymphoid tissues

Sinomenine (SIN) has long been used as a therapeutic agent of rheumatoid arthritis (RA) in China. However, the discrepancy between low oral bioavailability and higher minimal effective concentration made its action mode mysterious. The present study aimed to gain insight into the mechanisms by which SIN suppressed collagen-induced arthritis (CIA) in rats in view of Th17 and regulatory T (Treg) cell balance. SIN was orally administered, and the clinical symptoms of CIA rats were monitored; inflammatory cytokines levels in serum were measured by ELISA; pharmacokinetic studies were performed in normal and CIA rats; Th17 and Treg cell frequencies were analyzed by flow cytometry. The data showed that SIN treatment resulted in a dramatic decrease of arthritis scores and paw volume of CIA rats, which was accompanied by down-regulation of IL-17A and up-regulation of IL-10 in rat serum. The frequency of Treg cells was increased and the frequency of Th17 cells was decreased in the gut lymphoid tissues of SIN-treated rats. Immunohistochemistry assay demonstrated that more α4β7-positive cells were detained in joint tissues after SIN treatment. Moreover, the anti-arthritis efficacy of SIN disappeared when it was given by intraperitoneal injection, further confirming the action of SIN was gut-dependent. In conclusion, SIN exerts anti-RA action probably through modulating the frequencies of Treg cells and Th17 cells in intestinal lymph nodes and yielding a trafficking of lymphocytes (especially Treg cells) from gut to joint.

ApoA-IV: current and emerging roles in intestinal lipid metabolism, glucose homeostasis, and satiety.

Apolipoprotein A-IV (apoA-IV) is secreted by the small intestine on chylomicrons into intestinal lymph in response to fat absorption. Many physiological functions have been ascribed to apoA-IV, including a role in chylomicron assembly and lipid metabolism, a mediator of reverse-cholesterol transport, an acute satiety factor, a regulator of gastric function, and, finally, a modulator of blood glucose homeostasis. The purpose of this review is to update our current view of intestinal apoA-IV synthesis and secretion and the physiological roles of apoA-IV in lipid metabolism and energy homeostasis, and to underscore the potential for intestinal apoA-IV to serve as a therapeutic target for the treatment of diabetes and obesity-related disease.

Low-dose cyclophosphamide improves survival in a murine treatment model of sepsis.

Sepsis is a complex medical condition characterized by a systemic inflammatory response in the setting of infection. We hypothesized that combining antibiotics plus an immunosuppressant would protect against the morbidity and mortality of polymicrobial sepsis in mice better than would antibiotics alone. We used a murine cecal-ligation-and-puncture model in which mice were treated either with imipenem plus cyclophosphamide or imipenem alone. Titration to a low cyclophosphamide dose revealed that combination therapy increased survival by 20% compared with imipenem alone (56% vs. 36%, P < 0.001). To investigate the mechanism by which combination therapy did this, we reviewed quantitative and qualitative markers of the systemic immune response, end-organ damage, and the local immune response at the site of injury. Cyclophosphamide treatment was not associated with depletion of peripheral leukocytes or differences in pulmonary damage. However, mice that received combination therapy had higher plasma granulocyte colony-stimulating factor levels than did those treated with antibiotics alone. In addition, mice treated with cyclophosphamide had higher levels of bacterial colonization in intestinal Peyer's patch lymph nodes at 72 h after the septic insult. Intraperitoneal macrophage phenotypes and phagocytosis activity did not differ between groups. We conclude that the inflammatory response plays a significant role in the mortality of polymicrobial sepsis and that the regulation of this element is both feasible and beneficial in this disease model.

Spinal Burkitt's Lymphoma Mimicking Dumbbell Shape Neurogenic Tumor: A Case Report and Review of the Literature.

Non-Hodgkin's lymphoma (NHL), a disease which may involve the spine, is frequently associated with advanced disease. Radiculopathy caused by spinal root compression as the initial presentation in patients with NHL is very rare and thought to occur in less than 5% of cases. A 69-year-old woman complained of a history of low back pain with right sciatica for 1 month prior to admission. Computed tomography and magnetic resonance imaging of the lumbar spine showed a dumbbell-shape epidural mass lesion extending from L2 to L3, which was suggestive of a neurogenic tumor. After paraspinal approach and L2 lower half partial hemilaminectomy, total excision of the tumor was achieved, followed by rapid improvement of back pain and radiating pain. The lesion was confirmed to be Burkitt's lymphoma by histopathological examination. We then checked whole-body PET-CT, which showed multifocal malignant lesions in the intestine, liver, bone and left supraclavicular lymph node. Although a rare situation, Burkitt's lymphoma should be considered in the differential diagnosis for patients presenting with back and lumbar radicular pain without a prior history of malignancy. Burkitt's lymphoma could be the cause of dumbbell-shape spinal tumor.

Chylothorax: Percutaneous Embolization of the Thoracic Duct

Thoracic duct embolization is a percutaneous, image-guided intervention used in the management of chylothorax. Chylothorax, or chylous leak in the chest, is a rare condition that represents a spectrum of disorders that have in common leakage of intestinal lymph (chyle) into the thorax. Although conservative and surgical management are the standard of care, we present an overview of lymphangiography and percutaneous thoracic duct embolization.

Norisoboldine ameliorates collagen-induced arthritis through regulating the balance between Th17 and regulatory T cells in gut-associated lymphoid tissues

Norisoboldine (NOR), the main active ingredient of the dry root of Lindera aggregata, was previously proven to have substantial therapeutic effects on collagen-induced arthritis (CIA) in mice by oral administration. However, it exhibited a very poor bioavailability in normal rats. The pharmacokinetic–pharmacodynamics disconnection attracts us to explore its anti-arthritic mechanism in more detail. In this study, NOR, administered orally, markedly attenuated the pathological changes in CIA rats, which was accompanied by the down-regulation of pro-inflammatory cytokines and the up-regulation of anti-inflammatory cytokine IL-10. Pharmacokinetic studies demonstrated that the plasma concentration of NOR was moderately elevated in CIA rats compared with normal rats, but it was still far lower than the minimal effective concentration required for inhibiting the proliferation and activation of T lymphocytes in vitro. Interestingly, NOR was shown to regulate the balance between Th17 and regulatory T (Treg) cells in the intestinal lymph nodes more strikingly than in other tissues. It could increase the expression of Foxp3 mRNA in both gut and joints, and markedly up-regulate the number of integrin α4β7 (a marker of gut source)-positive Foxp3+ cells in the joints of CIA rats. These results suggest that the gut might be the primary action site of NOR, and NOR exerts anti-arthritis effect through regulating the balance between Th17 and Treg cells in intestinal lymph nodes and yielding a trafficking of lymphocytes (especially Treg cells) from the gut to joint. The findings of the present study also provide a plausible explanation for the anti-arthritic effects of poorly absorbed compounds like NOR.

Exploring the impact of drug properties on the extent of intestinal lymphatic transport - in vitro and in vivo studies.

Intestinal lymphatic transport of specific lipophilic drugs offers therapeutic advantages and maximises oral bioavailability. The aims of this study were; to compare intestinal lymphatic transport of a range of drugs and to investigate the influence of cyclosporine A on the mechanism/extent of lymphatic transport. Caco2 cells and an anaesthetised mesenteric lymphatic cannulated rat model were used for in vitro and in vivo studies. Lymphatic transport of three lipophilic drugs was directly compared in a long chain fatty acid formulation. In addition, the impact of cyclosporine A on triglyceride turnover was evaluated in vivo and in vitro. The extent of intestinal lymphatic transport in rats was positively correlated with drug solubility in triglyceride and negatively correlated with drug aqueous solubility. Cyclosporine A displayed non-linear lymphatic transport kinetics and reduced intestinal lymph triglyceride. In vitro experiments indicated that the cellular processes affected were intracellular lipid processing and/or lipid secretion. The linear correlations obtained using a range of lipophilic drugs confirm that the simplified approach of determining aqueous or triglyceride drug solubility is useful in predicting the extent of lymphatic transport. In vitro experiments correlated with in vivo observations, demonstrating the usefulness of the Caco-2 model for mechanistic investigations.

Functional differentiation of RAMP2 and RAMP3 in their regulation of the vascular system

Adrenomedullin (AM) is a vasoactive peptide that possesses various bioactivities. AM receptors are dimers consisting of CLR with one of two accessory proteins, RAMP2 or RAMP3. The functional difference between CLR/RAMP2 and CLR/RAMP3 and the relationship between the two receptors remain unclear. To address these issues, we generated RAMP2 and RAMP3 knockout (−/−) mice and have been studying their physiological activities in the vascular system. AM−/− and RAMP2−/− mice die in utero due to blood vessel abnormalities, which is indicative of their essential roles in vascular development. In contrast, RAMP3−/− mice were born normally without any major abnormalities. In adult RAMP3−/− mice, postnatal angiogenesis was normal, but lymphangiography using indocyanine green (ICG) showed delayed drainage of subcutaneous lymphatic vessels. Moreover, chyle transport by intestinal lymphatics was delayed in RAMP3−/− mice, which also showed more severe interstitial edema than wild-type mice in a tail lymphedema model, with characteristic dilatation of lymphatic capillaries and accumulation of inflammatory cells. In scratch-wound assays, migration of isolated RAMP3−/− lymphatic endothelial cells was delayed as compared to wild-type cells, and AM administration failed to enhance the re-endothelialization. The delay in re-endothelialization was due to a primary migration defect rather than a decrease in proliferation. These results suggest that RAMP3 regulates drainage through lymphatic vessels, and that the AM–RAMP3 system could be a novel therapeutic target for controlling postoperative lymphedema.

Intestinal translocation of clinical isolates of vancomycin-resistant Enterococcus faecalis and ESBL-producing Escherichia coli in a rat model of bacterial colonization and liver ischemia/reperfusion injury.

The objectives of this study were to develop a rat model of gastrointestinal colonization with vancomycin-resistant Enterococcus faecalis (VRE) and extended-spectrum beta-lactamase (ESBL)-producing E. coli and to evaluate intestinal translocation to blood and tissues after total and partial hepatic ischemia. Methods - We developed a model of rat colonization with VRE and ESBL-E coli. Then we studied four groups of colonized rats: Group I (with hepatic pedicle occlusion causing complete liver ischemia and intestinal stasis); Group II (with partial liver ischemia without intestinal stasis); Group III (surgical manipulation without hepatic ischemia or intestinal stasis); Group IV (anesthetized without surgical manipulation). After sacrifice, portal and systemic blood, large intestine, small intestine, spleen, liver, lungs, and cervical and mesenteric lymph nodes were cultured. Endotoxin concentrations in portal and systemic blood were determined. Results – The best inocula were: VRE: 2.4×1010 cfu and ESBL-E. coli: 1.12×1010 cfu. The best results occurred 24 hours after inoculation and antibiotic doses of 750 µg/mL of water for vancomycin and 2.1 mg/mL for ceftriaxone. There was a significantly higher proportion of positive cultures for ESBL-E. coli in the lungs in Groups I, II and III when compared with Group IV (67%; 60%; 75% and 13%, respectively; p:0.04). VRE growth was more frequent in mesenteric lymph nodes for Groups I (67%) and III (38%) than for Groups II (13%) and IV (none) (p:0.002). LPS was significantly higher in systemic blood of Group I (9.761±13.804 EU/mL−p:0.01). No differences for endotoxin occurred in portal blood. Conclusion –We developed a model of rats colonized with resistant bacteria useful to study intestinal translocation. Translocation occurred in surgical procedures with and without hepatic ischemia-reperfusion and probably occurred via the bloodstream. Translocation was probably lymphatic in the ischemia-reperfusion groups. Systemic blood endotoxin levels were higher in the group with complete hepatic ischemia.

Expression of Treg subsets on intestinal T cell immunity and endotoxin translocation in porcine sepsis after severe burns.

In the present study, the changes of the regulatory T cells (Treg) expression, endotoxin translocation, and the relationships in intestinal lymph nodes were investigated in porcine sepsis induced by severe burns. Flow cytometry, western blot, and Tachypleus amebocyte lysate were applied to study after the burn injury model was built. We found that the upregulated Treg expression was negatively related to the CD3(+)CD4(+)/CD3(+)CD8(+) ratio (r = -0.832, P < 0.05) after burn injury-induced sepsis. While Treg expression and portal venous plasma endotoxin translocation levels were positively correlated (r = 0.876, P < 0.05) when compared with the control group. Moreover, we detected a transforming of T cell subsets from T helper 1 cells to T helper 2 cells. Therefore, intestinal Treg cells expression exerts immunosuppressive effects on other intestinal T lymphocytes and was closely related to endotoxin translocation in porcine sepsis after severe burns injuries. Above all, the intestinal Treg cells may play an important role in the intestinal immune barrier system after severe burns injuries.

ASCITIS QUILOSA ASOCIADA A PANCREATITIS AGUDA

Chylous ascites associated with acute pancreatitis Background: Chylous ascites is defined as the presence of thoracic or intestinal lymph in the abdomi nal cavity. Its association with acute pancreatitis is uncommon. Aim: To report three cases of chilous ascites related with acute pancreatitis. Material and Methods: Review of medical records of three patients with chylous ascites associated with acute pancreatitis. Results: We report three patients with chylous ascites out of 2,188 admissions for acute pancreatitis (0.13%). A 39 years old male with a pancreatic pseudocyst. During surgery, chylous ascites was found. He was successfully treated with octreotide and spironolactone. A 71 years male operated for an acute cholecystitis and a perivesicular abscess. Three days after surgery, a chylous fluid appears in the abdominal drainage, which disappears spontaneously. A 73 years old female operated for an acute pancreatitis. During surgery a chylous ascites is found. The patient died four days after surgery. Conclusions: Chylous ascites associated with pancreatitis is uncommon and octreotide may have a therapeutic role for it.

Presence and persistence of Mycobacterium avium and other nontuberculous mycobacteria in animal tissues and derived foods: A review

Nontuberculous mycobacteria (NTM) are ubiquitous, potentially pathogenic organisms that have been isolated from a variety of environmental sources. NTM have been isolated from various kinds of food and many studies support the hypothesis that food, especially raw or partially cooked products, plays a role as a source of NTM for humans. Animals with disseminated infection have been diagnosed with NTM not only in the gastro-intestinal tract and intestinal lymph nodes, but also in tissues like muscle and parenchymatous organs. Infected animals may harbor NTM in their tissues even without clinical symptoms and especially minced meat with the possible addition of lymph nodes are considered as potential source of NTM. The purpose of this paper was to review articles concerning the detection of mycobacteria in the muscle tissue and lymph nodes of domestic animals, farmed and free-living game and to summarize methods and techniques for their detection.

Efferent intestinal lymph protein responses in nematode-resistant, -resilient and -susceptible lambs under challenge with Trichostrongylus colubriformis.

Breeding lines of sheep with resistance (R), resilience (Ri) or susceptibility (S) to nematode infections provide an experimental model to examine the biological mechanisms underlying the ability of some sheep to expel worms and remain healthy without the use of an anthelmintic. Using proteomics we identified differences in the expression of acute phase lymph proteins in the R, Ri and S lambs. The results will assist the development of alternative control strategies to manage nematode infections in livestock.

PPARβ/δ activation of CD300a controls intestinal immunity.

Macrophages are important for maintaining intestinal immune homeostasis. Here, we show that PPARβ/δ (peroxisome proliferator-activated receptor β/δ) directly regulates CD300a in macrophages that express the immunoreceptor tyrosine based-inhibitory motif (ITIM)-containing receptor. In mice lacking CD300a, high-fat diet (HFD) causes chronic intestinal inflammation with low numbers of intestinal lymph capillaries and dramatically expanded mesenteric lymph nodes. As a result, these mice exhibit triglyceride malabsorption and reduced body weight gain on HFD. Peritoneal macrophages from Cd300a−/− mice on HFD are classically M1 activated. Activation of toll-like receptor 4 (TLR4)/MyD88 signaling by lipopolysaccharide (LPS) results in prolonged IL-6 secretion in Cd300a−/− macrophages. Bone marrow transplantation confirmed that the phenotype originates from CD300a deficiency in leucocytes. These results identify CD300a-mediated inhibitory signaling in macrophages as a critical regulator of intestinal immune homeostasis.

High expression of RNA-binding motif protein 3 in esophageal and gastric adenocarcinoma correlates with intestinal metaplasia-associated tumours and independently predicts a reduced risk of recurrence and death.

BackgroundHigh nuclear expression of the RNA-binding motif protein 3 (RBM3) has previously been found to correlate with favourable clinicopathological characteristics and a prolonged survival in several cancer forms. Here, we examined the clinicopathological correlates and prognostic significance of RBM3 expression in tumours from a consecutive cohort of upper gastrointestinal adenocarcinoma.Material and methodsImmunohistochemical RBM3 expression was analysed in tissue microarrays with primary radiotherapy- and chemotherapy-naive adenocarcinoma of the esophagus, gastroesophageal junction and stomach (n = 173). In addition paired samples of normal squamous epithelium (n = 53), gastric mucosa (n = 117), Barrett’s esophagus/gastric intestinal metaplasia (n = 61) and lymph node metastases (n = 71) were analysed. Kaplan-Meier analysis and Cox proportional hazards modelling was applied to assess the impact of RBM3 expression on overall survival (OS) and recurrence-free survival (RFS).ResultsRBM3 expression was similar in primary tumours and lymph node metastases, but significantly higher in primary tumours and metastases arising in a background of intestinal metaplasia compared with cases without intestinal metaplasia (p < 0.001). RBM3 expression was significantly reduced in more advanced tumour stages (p = 0.006). Low RBM3 expression was significantly associated with a shorter OS in cases with radically resected (R0) tumours (HR 2.19, 95% CI 1.33-3.61, p = 0.002) and RFS in curatively treated patients with R0 resection/distant metastasis-free disease (HR = 3.21, 95% CI 1.64-6.30, p = 0.001). These associations remained significant in adjusted analysis (HR = 1.95, 95% CI 1.17-3.25, p = 0.010 for OS and HR = 3.02, 95% CI 1.45-6.29, p = 0.003 for RFS).ConclusionHigh expression of RBM3 may signify a subset of upper gastrointestinal cancers arising in a background of intestinal metaplasia and independently predicts a reduced risk of recurrence and death in patients with these cancer forms. These findings are of potential clinical utility and merit further validation.

Mesenteric lymph reperfusion after superior mesenteric artery occlusion shock exacerbates endotoxin translocation in brain.

To determine the role of mesenteric lymph reperfusion (MLR) on endotoxin translocation in brain to discuss the mechanism of brain injury subjected to superior mesenteric artery occlusion (SMAO) shock. Twenty-four rats were randomly assigned to MLR, SMAO, MLR+SMAO and sham groups. MLR was performed by clamping the mesenteric lymph duct (MLD) for 1 h and then allowing reperfusion for 2 h in the MLR group; SMAO involved clamping the superior mesenteric artery (SMA) for 1 h, followed by reperfusion for 2 h in the SMAO group; occlusion of both the SMA and MLD for 1 h was followed by reperfusion for 2 h in the MLR+SMAO group rats. SMAO shock induced severe increased levels of the endotoxin, lipopolysaccharide receptor, lipopolysaccharide-binding protein, intercellular adhesion molecule-1 and tumor necrosis factor-α. Concurrently, MLR after SMAO shock further aggravates these deleterious effects. Mesenteric lymph reperfusion exacerbated the endotoxin translocation in brain; thereby increased inflammatory response occurred, suggesting that the intestinal lymph pathway plays an important role in the brain injury after superior mesenteric artery occlusion shock.

Lymph-borne CD8α+ dendritic cells are uniquely able to cross-prime CD8+ T cells with antigen acquired from intestinal epithelial cells.

Cross-presentation of cellular antigens is crucial for priming CD8+ T cells, and generating immunity to intracellular pathogens—particularly viruses. It is unclear which intestinal phagocytes perform this function in vivo. To address this, we examined dendritic cells (DCs) from the intestinal lymph of IFABP-tOVA 232-4 mice, which express ovalbumin in small intestinal epithelial cells (IECs). Among lymph DCs (LDCs) only CD103+ CD11b− CD8α+ DCs cross-present IEC-derived ovalbumin to CD8+ OT-I T cells. Similarly, in the mesenteric lymph nodes (MLNs), cross-presentation of IEC–ovalbumin was limited to the CD11c+ MHCIIhi CD8α+ migratory DCs, but absent from all other subsets, including the resident CD8αhi DCs. Crucially, delivery of purified CD8α+ LDCs, but not other LDC subsets, into the MLN subcapsular lymphatic sinus induced proliferation of ovalbumin-specific, gut-tropic CD8+ T cells in vivo. Finally, in 232-4 mice treated with R848, CD8α+ LDCs were uniquely able to cross-prime interferon γ-producing CD8+ T cells and drive their migration to the intestine. Our results clearly demonstrate that migrating CD8α+ intestinal DCs are indispensable for cross-presentation of cellular antigens and, in conditions of inflammation, for the initial differentiation of effector CD8+ T cells. They may therefore represent an important target for the development of antiviral vaccinations.