Effector and Naturally Occurring Regulatory T Cells Display No Abnormalities in Activation Induced Cell Death in NOD Mice

BACKGROUND: Disturbed peripheral negative regulation might contribute to evolution of autoimmune insulitis in type 1 diabetes. This study evaluates the sensitivity of naïve/effector (Teff) and regulatory T cells (Treg) to activation-induced cell death mediated by Fas cross-linking in NOD and wild-type mice. PRINCIPAL FINDINGS: Both effector (CD25(-), FoxP3(-)) and suppressor (CD25(+), FoxP3(+)) CD4(+) T cells are negatively regulated by Fas cross-linking in mixed splenocyte populations of NOD, wild type mice and FoxP3-GFP trangeneess. Proliferation rates and sensitivity to Fas cross-linking are dissociated in Treg cells: fast cycling induced by IL-2 and CD3/CD28 stimulation improve Treg resistance to Fas-ligand (FasL) in both strains. The effector and suppressor CD4(+) subsets display balanced sensitivity to negative regulation under baseline conditions, IL-2 and CD3/CD28 stimulation, indicating that stimulation does not perturb immune homeostasis in NOD mice. Effective autocrine apoptosis of diabetogenic cells was evident from delayed onset and reduced incidence of adoptive disease transfer into NOD.SCID by CD4(+)CD25(-) T cells decorated with FasL protein. Treg resistant to Fas-mediated apoptosis retain suppressive activity in vitro. The only detectable differential response was reduced Teff proliferation and upregulation of CD25 following CD3-activation in NOD mice. CONCLUSION: These data document negative regulation of effector and suppressor cells by Fas cross-linking and dissociation between sensitivity to apoptosis and proliferation in stimulated Treg. There is no evidence that perturbed AICD in NOD mice initiates or promotes autoimmune insulitis

Association of CTLA-4 gene microsatellite polymorphism with ulcerative colitis in Chinese patients

Ulcerative colitis (UC) is characterized by chronic intestinal inflammation as a result of an exaggerated T cell response. Cytotoxic T lymphocyte associated antigen-4 (CTLA-4), expressed mainly in activated T cells, inhibits T cell activation and proliferation by combining B7 through competing CD28 and maintains immune homeostasis. Polymorphisms of the CTLA-4 gene are known to be associated with several autoimmune diseases. The aim of this study was to investigate the association between the CTLA-4 gene micro satellite polymorphism and UC in Chinese patients. Unrelated 100 Chinese patients with UC and 140 healthy controls were studied. The (AT) repeats in the 3′ untranslated region of exon 4 of the CTLA-4 gene were amplified by allele-specific polymerase chain reaction (PCR). The amplified products were electrophoresed on a 12% polyacrylamide gel, followed by silver staining. Twenty alleles were found in Chinese patients and healthy controls. The 122-bp allele was increased in UC compared with healthy controls (9.5% vs 0.7%, P = 0.0001/Pc = 0.002, OR = 14.591, 95% CI 3.357-63.420). The frequency of the longer alleles (≥118 bp) of UC was higher than that in healthy controls (26% vs 4%, P = 0.0001/Pc = 0.0002, OR = 7.644, 95%CI 3.950-14.792), but was not associated with location and severity of the disease. Furthermore, the longer alleles were not associated with haplotypes of C-318T/A+49G of the CTLA-4 gene in Chinese patients with UC. The longer alleles of the CTLA-4 gene microsatellite polymorphism were strongly associated with UC in Chinese patients. Copyright © 2006 by Lippincott Williams & Wilkins.link_to_subscribed_fulltex

Review of Underwater and In-Air Sounds Emitted by Australian and Antarctic Marine Mammals

The study of marine soundscapes is a growing field of research. Recording hardware is becoming more accessible; there are a number of off-the-shelf autonomous recorders that can be deployed for months at a time; software analysis tools exist as shareware; rawor preprocessed recordings are freely and publicly available. However, what is missing are catalogues of commonly recorded sounds. Sounds related to geophysical events (e.g. earthquakes) and weather (e.g. wind and precipitation), to human activities (e.g. ships) and to marine animals (e.g. crustaceans, fish and marine mammals) commonly occur. Marine mammals are distributed throughout Australia's oceans and significantly contribute to the underwater soundscape. However, due to a lack of concurrent visual and passive acoustic observations, it is often not known which species produces which sounds. To aid in the analysis of Australian and Antarctic marine soundscape recordings, a literature review of the sounds made by marine mammals was undertaken. Frequency, duration and source level measurements are summarised and tabulated. In addition to the literature review, new marine mammal data are presented and include recordings from Australia of Omura's whales (Balaenoptera omurai), dwarf sperm whales (Kogia sima), common dolphins (Delphinus delphis), short-finned pilot whales (Globicephala macrorhynchus), long-finned pilot whales (G. melas), Fraser's dolphins (Lagenodelphis hosei), false killer whales (Pseudorca crassidens), striped dolphins (Stenella coeruleoalba) and spinner dolphins (S. longirostris), as well as the whistles and burst-pulse sounds of Australian pygmy killer whales (Feresa attenuata). To date, this is the most comprehensive acoustic summary for marine mammal species in Australian waters