AbstractCover imageThe cover image depicts human intestinal microvascular endothelial cells stained for ICAM‐1 after in vitro stimulation with the pro‐inflammatory cytokine TNF‐α. The image was taken from a recently‐published article by Scaldaferri et al. (Eur. J. Immunol. 2009. 39: 290–300), in which the authors demonstrate that stimulation with TNF‐α up‐regulates ICAM‐1 expression in human intestinal microvascular endothelial cells leading to increased recruitment of lymphocytes in the gut, a key pathogenic event in inflammatory bowel disease. magnified imageTreg‐mediated immune balance in malaria‐exposed populationspp. 1288–1300Much of the pathology caused by parasitic infections is immune related, and the outcome of infection depends on a delicate balance between pro‐inflammatory responses and regulatory mechanisms. In this issue, Finney et al. demonstrate a transient increase in the number and percentage of circulating FOXP3+ Treg in a human population exposed to malaria. Importantly, Treg numbers mirror the expansion and contraction of T effector cells with Treg:T effector ratios remaining remarkably stable over time, irrespective of age, season or local malaria endemicity. The seasonal changes in Treg numbers, together with its pro‐apoptotic phenotype, suggest that Treg are induced – and/or proliferate – in response to rising T‐cell numbers and contract by apoptosis when T effector cell activity returns to baseline. The data represent a clear example of in vivo induction/expansion of Treg in proportion to effector T cells in order to maintain immune homeostasis. magnified imageThe theatre of autoimmune diabetes: The lymph node is not the only stagepp. 1313–1322Treg inhibit progression of autoimmune diabetes; while the phenomenon is well recognized, the mechanism is poorly understood. Co‐transfer of antigen‐specific Treg suppresses diabetes induced by adoptive transfer of beta cell auto‐antigen‐specific effector T cells; and indeed, several groups have demonstrated Treg activitiy in the pancreatic draining lymph node. In this issue, Tonkin et al. shed further light on the protective mechanism involved. Following T‐cell transfer, many islet‐specific Treg are found in the pancreas, which is accompanied by suppression of cytokines and chemokines produced by effector T cells and a reduced number of inflammatory macrophages. This protection was TGF‐β‐dependent, as demonstrated by transducing effector T cells with a dominant‐negative form of the TGF‐β receptor. Thus, in the theatre of autoimmune diabetes, the action takes place not only in the draining lymph node, but also in the pancreas. magnified imageFungal signal integration leads to Th17 responsespp. 1379–1386Appropriate integration of pathogen‐related signals is one key requirement for successful immune responses. In the case of fungal infections, fungal particles contain ligands for multiple TLR, as well as the beta‐glucan receptor, dectin‐1. In this issue, Dennehy et al. demonstrate how fungal particles mediate Th17 responses. The authors show that co‐ligation of MyD88‐coupled TLR and dectin‐1 enhances Th17‐related cytokines such as IL‐6 and IL‐23 and inhibits the Th1‐associated cytokine IL‐12. This is an excellent example of reciprocal cytokine response regulation and helps explain how the interaction of pattern recognition receptors can promote different types of immune responses magnified imageInduction of Th17 by Langerhans cellspp. 1221–1230Although a myriad of cytokines have been studied for their effects on induction, amplification and stabilization of the Th17 phenotype, the cellular sources of these Th17‐driving cytokines remain obscure. In the human epidermis, suprabasal located Langerhans cells (LC) constitutively release TGF‐β, which ensures the viability and immature state of LC, and conditional to skin barrier breakdown are LC exposed to direct bacterial contact. In this issue, Aliahmadi et al. show that only true LC, activated by TLR2 agonists, are able to secrete IL‐6, IL‐1β and IL‐23; these Langerin+ cells induce Th17 cells that secrete IL‐17A and express RORγt. Blocking TLR2 on LC completely inhibits polarization of Th cells. This study supports a role of TLR2 in eliciting Th17 immune responses in inflamed skin. magnified imageSuppressive HIV‐specific T cells contribute to the T‐cell immune dysfunction in HIV patientspp. 1280–1287During chronic HIV‐1 infection, persistent viral replication exhausts the immune system and leaves the host susceptible to opportunistic infections and malignancies. In this issue, Torheim et al. investigate whether populations of suppressive immune cells are present within the HIV‐specific T‐cell population. The authors isolate T cells secreting IL‐10 in response to HIV antigens by cell‐surface capture of the secreted cytokine followed by immunomagnetic cell‐sorting. These isolated IL‐10‐secreting T cells potently suppress polyclonal T‐cell expansion in co‐cultures. HIV‐specific T cells are important for containment of the virus and eradication of virus‐infected cells; the presence of T cells with immunosuppressive properties within the HIV‐specific T‐cell subset may limit the ability of the immune system to achieve viral control. Thus, HIV‐specific T cells that secrete IL‐10 upon antigenic activation may contribute to the immune deficiency that is observed in HIV patients. magnified image