Low-level regulatory T-cell activity is essential for functional type-2 effector immunity to expel gastrointestinal helminths.

Helminth infection is frequently associated with the expansion of regulatory T cells (Tregs) and suppression of immune responses to bystander antigens. We show that infection of mice with the chronic gastrointestinal helminth Heligmosomoides polygyrus drives rapid polyclonal expansion of Foxp3(+)Helios(+)CD4(+) thymic (t)Tregs in the lamina propria and mesenteric lymph nodes while Foxp3(+)Helios(-)CD4(+) peripheral (p)Treg expand more slowly. Notably, in partially resistant BALB/c mice parasite survival positively correlates with Foxp3(+)Helios(+)CD4(+) tTreg numbers. Boosting of Foxp3(+)Helios(+)CD4(+) tTreg populations by administration of recombinant interleukin-2 (rIL-2):anti-IL-2 (IL-2C) complex increased worm persistence by diminishing type-2 responsiveness in vivo, including suppression of alternatively activated macrophage and granulomatous responses at the sites of infection. IL-2C also increased innate lymphoid cell (ILC) numbers, indicating that Treg functions dominate over ILC effects in this setting. Surprisingly, complete removal of Tregs in transgenic Foxp3-DTR mice also resulted in increased worm burdens, with "immunological chaos" evident in high levels of the pro-inflammatory cytokines IL-6 and interferon-γ. In contrast, worm clearance could be induced by anti-CD25 antibody-mediated partial depletion of early Treg, alongside increased T helper type 2 responses and without incurring pathology. These findings highlight the overarching importance of the early Treg response to infection and the non-linear association between inflammation and the prevailing Treg frequency.

Four decades of conjoined twins at Red Cross Children's Hospital--lessons learned.

Conjoined twins represent a rare but fascinating congenital condition, the aetiology of which remains obscure. Over the past four decades, the paediatric surgeons at Red Cross Children's Hospital have been involved in the management of 46 pairs of conjoined twins, of which 33 have been symmetrical and 12 asymmetrical. Seventeen symmetrical twins have undergone separation with 22 children (65%) surviving; all of the live asymmetrical twins survived separation. We describe the important features of this unique cohort, outline our approach to management and present the results of this approach. We consider some of the ethical and moral dilemmas we have confronted, and discuss the prenatal diagnosis, obstetric implications and postnatal care of these children, including the relevant investigations and anaesthetic and surgical management. Specific aspects related to the cardiovascular system, hepatobiliary and gastrointestinal tracts, urogenital tract, central nervous system and musculoskeletal system are highlighted.

Immunity induced by the radiation-attenuated schistosome vaccine.

As a paradigm for the development of a vaccine against human schistosomiasis, the radiation-attenuated (RA) vaccine has enabled the dissection of different immune responses as putative effector mechanisms. This review considers advances made in the past, and updates our knowledge with reference to recent studies that have provided new information relevant particularly to the early innate events after vaccination, and to the nature of the protective effector mechanism. Priming of a protective response by RA larvae is a highly co-ordinated series of events starting in the skin, draining lymph nodes and lungs, leading to the development of various effector responses, ranging from Th1-associated cell-mediated activity, to anti-parasitic antibodies, all of which contribute to the elimination of challenge larvae to varying extents. In this respect, the RA vaccine elicits a multifaceted immune response, from which we can derive valuable insights relevant to the future design of novel delivery systems and adjuvants for recombinant and subunit vaccines.

Modulation of the host's immune response by schistosome larvae.

Schistosomes appear to have evolved several strategies to down-regulate the host's immune response in order to promote their own survival. For the host, down-regulation is also beneficial as it can limit the extent of pathology. It is widely accepted that schistosomes modulate the immune response during the chronic phase of infection after egg deposition has started. However, there is increasing evidence that modulation of the immune response can occur much earlier at the time infective cercariae penetrate the host skin. In this review, we explore the various lines of evidence that excretory/secretory (ES) molecules from cercariae down-regulate the host's immune response. We highlight the immunological factors that are produced and may be involved in regulating the immune system (e.g. IL-10, and eicosanoids), as well as speculating on possible mechanisms of immune modulation (e.g. mast-cell activation, T-cell apoptosis, and/or the skewed activation of antigen-presenting cells [APCs]). Finally, we draw attention to several molecules of schistosome origin that have the potential to stimulate the regulatory response (e.g. glycans) and link these to potential host receptors (e.g. TLRs and C-type lectins).

Role of thoracic surgery for childhood tuberculosis.

Lymphadenopathy is the hallmark of intrathoracic tuberculosis in children. The role of the thoracic surgeon in treating childhood tuberculosis is to relieve the more severe symptoms of lymphadenopathy, prevent the more long-term secondary damage that lymphadenopathy may cause to the lung, and treat the sequelae of thoracic tuberculosis. We reviewed the role of surgery in childhood tuberculosis at Red Cross Children Hospital from January 1981 to January 1996 in 161 children under 13 who were admitted for 168 therapeutic surgical interventions for proved intrathoracic tuberculosis and its related complications. We classified patients according to the pathophysiology of their disease to clarify the role of surgery in their management. Successful decompression of lymph nodes that were acutely compromising major airways was done in 25 children, and decompression for chronic airway compression was successful in 8 of 11 children. Therapeutic bronchoscopy successfully opened an airway obstructed by intraluminal tissue in 68% of 28 patients, with long-term pulmonary reexpansion in 50%. Pulmonary resections for postprimary tuberculous damage were done in 72 patients with a mortality of 2.7% and morbidity of 16.7%. Another 17 patients were operated on for pleural disease and 15 for other tuberculosis-related problems. The mortality for all patients undergoing surgery for complications of tuberculosis during childhood was 1.9% (3/161), suggesting that when indicated, an aggressive surgical approach is relatively safe.