When intracellular pathogens invade mammalian hosts, naïve CD8+ T cells differentiate into cytotoxic killers, which lyse infected target cells and secrete cytokines that activate intracellular microbicides. We show that CD8+ T cells deficient in the transcription factors T-bet and eomesodermin (Eomes) fail to differentiate into functional killers required for defense against lymphocytic choriomeningitis virus. Instead, virus-specific CD8+ T cells lacking both T-bet and Eomes differentiate into an interleukin-17–secreting lineage, reminiscent of the helper T cell fate that has been implicated in autoimmunity and extracellular microbial defense. Upon viral infection, mice with T cells lacking both T-bet and Eomes develop a CD8+ T cell–dependent, progressive inflammatory and wasting syndrome characterized by multi-organ infiltration of neutrophils. T-bet and Eomes, thus, ensure that CD8+ T cells adopt an appropriate course of intracellular rather than extracellular destruction.

Inflammation is characterized by pain, localized swelling, heat, redness and a loss of function. The inflammatory stage typically lasts around 5 days and all treatment during this time is designed to address the cardinal signs of inflammation � pain, s...

Inflammation mediated by antibody-antigen complexes contributes to autoimmune diseases. Mice deficient in the common Fcγ-chain are protected from IgG-mediated glomerulonephritis and the reverse passive Arthus (RPA) reaction and FcR-bearing macrophages, and mast cells have been assigned primary roles in these processes. Here we demonstrate that neutrophil-selective transgenic expression of the two uniquely human neutrophil Fc gamma receptors (FcγRs), FcγRIIA and FcγRIIIB, in Fcγ-chain-deficient mice restored susceptibility to progressive glomerulonephritis and the cutaneous RPA reaction. FcγRIIIB and FcγRIIA mediated neutrophil accumulation, whereas FcγRIIA alone promoted organ injury. In a model of soluble immune complexes deposited within the vasculature, FcγRIIIB was responsible for neutrophil slow rolling and adhesion whereas in the cremaster RPA, induced by both vascular and tissue soluble immune complexes, FcγRIIA predominated. Thus, human FcγRs on neutrophils serve as molecular links between antibody and immunological disease, with FcγRIIA promoting tissue injury and FcγRIIIB and FcγRIIA displaying specialized context-dependent functions in neutrophil recruitment.

The objective of this study was to test the hypothesis that the inflammatory response to a high-fat, low-carbohydrate weight loss diet (HF) we previously observed was due to oxidative stress. Nineteen overweight subjects (BMI > 27 kg/m2) were randomly assigned to either an antioxidant supplement (AS) (1 g vitamin C/800 IU vitamin E) or a placebo (P) group and provided with a HF for 7 days. Fasted pre- and post serum samples were measured for markers of inflammation (C-reactive protein (CRP), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1)), oxygen radical absorbance capacity (ORAC), and glucose, whereas urine was measured for oxidative stress (8-epi-prostaglandin-F2(8-epi)). HF resulted in significant reductions in weight (-3.2%), glucose (-18.7%), and MCP-1 (-15%) (all P < 0.01), with no difference between groups. There was a trend for a differential effect between groups for CRP as it decreased 32% in the AS group but increased 50% for P (P = 0.076). Inverse correlations were noted between initial values and changes in several inflammatory and oxidative stress markers, including CRP (r = -0.501), 8-epi (r = -0.863), and ORAC (r = -0.546) (all P < 0.05). It was concluded that weight loss on a short-term HF caused reduction of some but not all markers of inflammation. A role for oxidative stress in causing inflammation was not confirmed; however, longer term diet-controlled studies are necessary to further explore the trend for a differential response in CRP with antioxidant supplementation.

Further support for the long-suspected link between inflammation and cancer is provided by two new studies. In the first study, scientists at the Massachusetts Institute of Technology (MIT), USA, report that chronic inflammation of the intestine or stomach can damage DNA, increasing the risk of cancer (The Journal of Clinical Investigation, 2 June 2008). Besides the suspected role for inflammatory cytokines in cancer, it is thought that reactive oxygen and nitrogen species released by inflammatory immune cells can damage DNA and contribute to cancer. To test this theory, the MIT researchers induced colon inflammation by administering a chemical compound to mice that lacked the normal machinery that repairs damaged DNA. "Lo and behold, the DNA repair deficient mice were more susceptible [to cancer]", said Lisiane Meira, the lead author of the study (ScienceDaily, 3 June 2008). Commenting on the link, Meira said, "It's something that was expected but it was never formally proven." (MIT News Office, 2 June 2008.) As the effectiveness of DNA repair systems can differ between individuals, such "variation could influence the susceptibility of individuals [to cancer] and how they are going to respond to a chronic inflammation response," said the senior author of the study Leona Samson (MIT News Office). In the second study, researchers at Imperial College London, UK, studied the health records of approx50,000 men and found a link between gum disease and cancer (Lancet Oncology, 6 May 2008). "Periodontal disease was significantly associated with an increased risk of lung, kidney, pancreatic and haematological cancers." (Telegraph, 26 May 2008.) The researchers suggested that the persistent presence of gum disease might be a sign of a weak immune system, which could also allow cancer to develop, or that the bacteria from the gums might directly cause cancer (BBC News, 26 May 2008).