T cells become licensed in the lung to enter the central nervous system.

The blood­brain barrier (BBB) and the environment of the central nervous system (CNS) guard the nervous tissue from peripheral immune cells. In the autoimmune disease multiple sclerosis, myelin-reactive T-cell blasts are thought to transgress the BBB and create a pro-inflammatory environment in the CNS, thereby making possible a second autoimmune attack that starts from the leptomeningeal vessels and progresses into the parenchyma. Using a Lewis rat model of experimental autoimmune encephalomyelitis, we show here that contrary to the expectations of this concept, T-cell blasts do not efficiently enter the CNS and are not required to prepare the BBB for immune-cell recruitment. Instead, intravenously transferred T-cell blasts gain the capacity to enter the CNS after residing transiently within the lung tissues. Inside the lung tissues, they move along and within the airways to bronchus-associated lymphoid tissues and lung-draining mediastinal lymph nodes before they enter the blood circulation from where they reach the CNS. Effector T cells transferred directly into the airways showed a similar migratory pattern and retained their full pathogenicity. On their way the T cells fundamentally reprogrammed their gene-expression profile, characterized by downregulation of their activation program and upregulation of cellular locomotion molecules together with chemokine and adhesion receptors. The adhesion receptors include ninjurin 1, which participates in T-cell intravascular crawling on cerebral blood vessels. We detected that the lung constitutes a niche not only for activated T cells but also for resting myelin-reactive memory T cells. After local stimulation in the lung, these cells strongly proliferate and, after assuming migratory properties, enter the CNS and induce paralytic disease. The lung could therefore contribute to the activation of potentially autoaggressive T cells and their transition to a migratory mode as a prerequisite to entering their target tissues and inducing autoimmune disease.

Field Evaluation of the Effectiveness of an Oral Toltrazuril and Iron Combination (Baycox® Iron) in Maintaining Weaning Weight by Preventing Coccidiosis and Anaemia in Neonatal Piglets.

Effectiveness of an oral combination of toltrazuril and iron dextran (Baycox(®) Iron) to maintain weaning weight by preventing coccidiosis caused by Isospora suis and iron-deficiency anaemia in neonatal piglets was investigated on three commercial pig farms with a history of coccidiosis: two in Mexico and one in Brazil. On day (SD) 2 of life, piglets were randomised within litter by bodyweight to treatment or control group. On SD 3 piglets allocated to the control group (CG) each received 1 mL Baycox(®), containing 50 mg/mL toltrazuril orally and commercially available iron (200 mg/piglet) by intramuscular injection. Piglets allocated to the treatment group (TG) each received 1 mL toltrazuril and iron combination orally (Baycox(®) Iron) containing 50 mg/mL toltrazuril and 228 mg iron as iron dextran. All piglets had access to creep feed. 6493 piglets completed the study. Bodyweight at weaning on SD 21 of piglets treated with the oral toltrazuril and iron combination was confirmed to be non-inferior to the control treatment with <1 % difference between group mean body weights. Faecal samples from at least 10 % of litters on SD 14 demonstrated control of coccidiosis. Haemoglobin levels on SD 21 were lower in the oral toltrazuril and iron combination treated piglets compared to control levels but above minimum haemoglobin levels to maintain health. There was no difference in mortality between the two groups. This large scale field evaluation clearly demonstrated the effectiveness of a combination of oral toltrazuril and iron (Baycox(®) Iron) in maintaining body weight at weaning compared to conventional treatment. The combination was effective in preventing coccidiosis and anaemia and thus provides a valuable alternative that reduces stressful events in neonatal piglets. There were no product related adverse events.

Instant effect of soluble antigen on effector T cells in peripheral immune organs during immunotherapy of autoimmune encephalomyelitis.

i.v. infusion of native autoantigen or its altered peptide variants is an important therapeutic option for the treatment of autoimmune diseases, because it selectively targets the disease-inducing T cells. To learn more about the mechanisms and kinetics of this approach, we visualized the crucial initial effects of i.v. infusion of peptides or intact protein on GFP-tagged autoaggressive CD4(+) effector T cells using live-video and two-photon in situ imaging of spleens in living animals. We found that the time interval between i.v. injection of intact protein to first changes in T cell behavior was extremely short; within 10 min after protein application, the motility of the T cells changed drastically. They slowed down and became tethered to local sessile stromal cells. A part of the cells aggregated to form clusters. Within the following 20 min, IFN-gamma mRNA was massively (>100-fold) up-regulated; surface IL-2 receptor and OX-40 (CD 134) increased 1.5 h later. These processes depleted autoimmune T cells in the blood circulation, trapping the cells in the peripheral lymphoid organs and thus preventing them from invading the CNS. This specific blockage almost completely abrogated CNS inflammation and clinical disease. These findings highlight the speed and efficiency of antigen recognition in vivo and add to our understanding of T cell-mediated autoimmunity.