Showing papers by "Karolinska Institutet published in 2000"

Environmental and Heritable Factors in the Causation of Cancer — Analyses of Cohorts of Twins from Sweden, Denmark, and Finland

Abstract: Background The contribution of hereditary factors to the causation of sporadic cancer is unclear. Studies of twins make it possible to estimate the overall contribution of inherited genes to the development of malignant diseases. Methods We combined data on 44,788 pairs of twins listed in the Swedish, Danish, and Finnish twin registries in order to assess the risks of cancer at 28 anatomical sites for the twins of persons with cancer. Statistical modeling was used to estimate the relative importance of heritable and environmental factors in causing cancer at 11 of those sites. Results At least one cancer occurred in 10,803 persons among 9512 pairs of twins. An increased risk was found among the twins of affected persons for stomach, colorectal, lung, breast, and prostate cancer. Statistically significant effects of heritable factors were observed for prostate cancer (42 percent of the risk may be explained by heritable factors; 95 percent confidence interval, 29 to 50 percent), colorectal cancer (35 perce...

Physiological functions of thioredoxin and thioredoxin reductase.

Abstract: Thioredoxin, thioredoxin reductase and NADPH, the thioredoxin system, is ubiquitous from Archea to man. Thioredoxins, with a dithiol/disulfide active site (CGPC) are the major cellular protein disulfide reductases; they therefore also serve as electron donors for enzymes such as ribonucleotide reductases, thioredoxin peroxidases (peroxiredoxins) and methionine sulfoxide reductases. Glutaredoxins catalyze glutathione-disulfide oxidoreductions overlapping the functions of thioredoxins and using electrons from NADPH via glutathione reductase. Thioredoxin isoforms are present in most organisms and mitochondria have a separate thioredoxin system. Plants have chloroplast thioredoxins, which via ferredoxin-thioredoxin reductase regulates photosynthetic enzymes by light. Thioredoxins are critical for redox regulation of protein function and signaling via thiol redox control. A growing number of transcription factors including NF-kappaB or the Ref-1-dependent AP1 require thioredoxin reduction for DNA binding. The cytosolic mammalian thioredoxin, lack of which is embryonically lethal, has numerous functions in defense against oxidative stress, control of growth and apoptosis, but is also secreted and has co-cytokine and chemokine activities. Thioredoxin reductase is a specific dimeric 70-kDa flavoprotein in bacteria, fungi and plants with a redox active site disulfide/dithiol. In contrast, thioredoxin reductases of higher eukaryotes are larger (112-130 kDa), selenium-dependent dimeric flavoproteins with a broad substrate specificity that also reduce nondisulfide substrates such as hydroperoxides, vitamin C or selenite. All mammalian thioredoxin reductase isozymes are homologous to glutathione reductase and contain a conserved C-terminal elongation with a cysteine-selenocysteine sequence forming a redox-active selenenylsulfide/selenolthiol active site and are inhibited by goldthioglucose (aurothioglucose) and other clinically used drugs.

The Vienna classification of gastrointestinal epithelial neoplasia

Abstract: Background—Use of the conventional Western and Japanese classification systems of gastrointestinal epithelial neoplasia results in large diVerences among pathologists in the diagnosis of oesophageal, gastric, and colorectal neoplastic lesions. Aim—To develop common worldwide terminology for gastrointestinal epithelial neoplasia. Methods—Thirty one pathologists from 12 countries reviewed 35 gastric, 20 colorectal, and 21 oesophageal biopsy and resection specimens. The extent of diagnostic agreement between those with Western and Japanese viewpoints was assessed by kappa statistics. The pathologists met in Vienna to discuss the results and to develop a new consensus terminology. Results—The large diVerences between the conventional Western and Japanese diagnoses were confirmed (percentage of specimens for which there was agreement and kappa values: 37% and 0.16 for gastric; 45% and 0.27 for colorectal; and 14% and 0.01 for oesophageal lesions). There was much better agreement among pathologists (71% and 0.55 for gastric; 65% and 0.47 for colorectal; and 62% and 0.31 for oesophageal lesions) when the original assessments of the specimens were regrouped into the categories of the proposed Vienna classification of gastrointestinal epithelial neoplasia: (1) negative for neoplasia/dysplasia, (2) indefinite for neoplasia/dysplasia, (3) non-invasive low grade neoplasia (low grade adenoma/ dysplasia), (4) non-invasive high grade neoplasia (high grade adenoma/ dysplasia, non-invasive carcinoma and suspicion of invasive carcinoma), and (5) invasive neoplasia (intramucosal carcinoma, submucosal carcinoma or beyond). Conclusion—The diVerences between Western and Japanese pathologists in the diagnostic classification of gastrointestinal epithelial neoplastic lesions can be resolved largely by adopting the proposed terminology, which is based on cytological and architectural severity and invasion status. (Gut 2000;47:251‐255)

Generalized potential of adult neural stem cells.

Abstract: The differentiation potential of stem cells in tissues of the adult has been thought to be limited to cell lineages present in the organ from which they were derived, but there is evidence that some stem cells may have a broader differentiation repertoire. We show here that neural stem cells from the adult mouse brain can contribute to the formation of chimeric chick and mouse embryos and give rise to cells of all germ layers. This demonstrates that an adult neural stem cell has a very broad developmental capacity and may potentially be used to generate a variety of cell types for transplantation in different diseases.

Pooled Analysis of Prospective Cohort Studies on Height, Weight, and Breast Cancer Risk

Abstract: The association between anthropometric indices and the risk of breast cancer was analyzed using pooled data from seven prospective cohort studies. Together, these cohorts comprise 337,819 women and 4,385 incident invasive breast cancer cases. In multivariate analyses controlling for reproductive, dietary, and other risk factors, the pooled relative risk (RR) of breast cancer per height increment of 5 cm was 1.02 (95% confidence interval (Cl): 0.96, 1.10) in premenopausal women and 1.07 (95% Cl: 1.03, 1.12) in postmenopausal women. Body mass index (BMI) showed significant inverse and positive associations with breast cancer among pre- and postmenopausal women, respectively; these associations were nonlinear. Compared with premenopausal women with a BMI of less than 21 kg/m2, women with a BMI exceeding 31 kg/m2 had an RR of 0.54 (95% Cl: 0.34, 0.85). In postmenopausal women, the RRs did not increase further when BMI exceeded 28 kg/m2; the RR for these women was 1.26 (95% Cl: 1.09, 1.46). The authors found little evidence for interaction with other breast cancer risk factors. Their data indicate that height is an independent risk factor for postmenopausal breast cancer; in premenopausal women, this relation is less clear. The association between BMI and breast cancer varies by menopausal status. Weight control may reduce the risk among postmenopausal women.

Mechanism of regulation of the hypoxia‐inducible factor‐1α by the von Hippel‐Lindau tumor suppressor protein

Abstract: In normoxic cells the hypoxia-inducible factor-1 alpha (HIF-1 alpha) is rapidly degraded by the ubiquitin-proteasome pathway, and activation of HIF-1 alpha to a functional form requires protein stabilization. Here we show that the product of the von Hippel-Lindau (VHL) tumor suppressor gene mediated ubiquitylation and proteasomal degradation of HIF-1 alpha under normoxic conditions via interaction with the core of the oxygen-dependent degradation domain of HIF-1 alpha. The region of VHL mediating interaction with HIF-1 alpha overlapped with a putative macromolecular binding site observed within the crystal structure of VHL. This motif of VHL also represents a mutational hotspot in tumors, and one of these mutations impaired interaction with HIF-1 alpha and subsequent degradation. Interestingly, the VHL binding site within HIF-1 alpha overlapped with one of the minimal transactivation domains. Protection of HIF-1 alpha against degradation by VHL was a multistep mechanism, including hypoxia-induced nuclear translocation of HIF-1 alpha and an intranuclear hypoxia-dependent signal. VHL was not released from HIF-1 alpha during this process. Finally, stabilization of HIF-1 alpha protein levels per se did not totally bypass the need of the hypoxic signal for generating the transactivation response.

Incidence of dementia and major subtypes in Europe: A collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group.

Abstract: The authors examined the association of incident dementia and subtypes with age, sex, and geographic area in Europe. Incidence data from eight population-based studies carried out in seven European countries were compared and pooled. The pooled data included 835 mild to severe dementia cases and 42,996 person-years of follow-up. In all studies a higher proportion of cases were diagnosed with AD (60 to 70% of all demented cases) than vascular dementia (VaD). The incidence of dementia and AD continued to increase with age up to age 85 years, after which rates increased in women but not men. There was a large variation in VaD incidence across studies. In the pooled analysis, the incidence rates increased with age without any substantial difference between men and women. Surprisingly, higher incidence rates of dementia and AD were found in the very old in northwest countries than in southern countries. This study confirms that AD is the most frequent dementing disorder in all ages, and that there is a higher incidence of dementia, specifically AD, in women than men among the very old. Finally, there may be regional differences in dementia incidence.

Impaired endochondral ossification and angiogenesis in mice deficient in membrane-type matrix metalloproteinase I

Abstract: Membrane-type matrix metalloproteinase I (MT1-MMP)-deficient mice were found to have severe defects in skeletal development and angiogenesis. The craniofacial, axial, and appendicular skeletons were severely affected, leading to a short and domed skull, marked deceleration of postnatal growth, and death by 3 wk of age. Shortening of bones is a consequence of decreased chondrocyte proliferation in the proliferative zone of the growth plates. Defective vascular invasion of cartilage leads to enlargement of hypertrophic zones of growth plates and delayed formation of secondary ossification centers in long bones. In an in vivo corneal angiogenesis assay, null mice did not have angiogenic response to implanted FGF-2, suggesting that the defect in angiogenesis is not restricted to cartilage alone. In tissues from null mice, activation of latent matrix metalloproteinase 2 was deficient, suggesting that MT1-MMP is essential for its activation in vivo.

Are there two types of malnutrition in chronic renal failure? Evidence for relationships between malnutrition, inflammation and atherosclerosis (MIA syndrome)

Abstract: Many methods have been used to assess the presence It is believed that malnutrition is common in patients with chronic renal failure (CRF). They have reduced of malnutrition in patients with CRF. A history of weight loss and symptoms such as anorexia, nausea body weight, depleted energy (fat tissue) stores, loss of somatic protein ( low muscle mass) and low levels of and vomiting may indicate impending or established malnutrition. Anthropometric measurements, such as serum albumin, transferrin, pre-albumin and other visceral proteins. Various studies show signs of malnumid-arm muscle circumference, skinfold thickness and hand-grip strength may all be useful tools for estimattrition in 23–76% of haemodialysis (HD) and 18–50% of peritoneal dialysis (PD) patients [1–4]. Such variing malnutrition. Hand-grip strength, in particular, has been shown to be an inexpensive, reliable and easily ations in the prevalence of malnutrition may be related to factors such as age, case mix, co-morbid conditions performed parameter of nutrition [4,8] that also predicts mortality in CRF patients (unpublished observaand quality of dialysis therapy. The aetiology of malnutrition in CRF is complex and may include many tion). Creatinine kinetics have also been advocated as a method to assess nutritional status. However, recent factors, e.g. poor food intake because of anorexia, nausea and vomiting due to uraemic toxicity, hormonal evidence suggests that it is unreliable in individual CRF patients [8,9]. More sophisticated methods used derangements, acidosis and increased resting energy expenditure. to evaluate nutritional status include bio-electrical impedance, dual-emission X-ray absorptiometry While malnutrition by definition is caused by poor nutritional intake, laboratory or anthropometric meas(DXA), nuclear magnetic resonance, computerized tomography, total body potassium and total body urements are generally used to define it clinically. Other factors can cause the same changes in body and plasma nitrogen, but mostly as research tools. Finally, several biochemical markers [e.g. serum albumin, pre-albumin, protein composition, especially inflammatory and infectious complications [5,6 ] and chronic heart failure insulin-like growth factor-1 (IGF-1) and transferrin] have been used to evaluate nutritional status. Of these (CHF). In addition, factors directly associated with the dialytic procedure, such as bio-incompatibility, biochemical markers, serum albumin so far has been the most common to assess malnutrition, and hyponutrient losses in the dialysate and, during PD, poor appetite due to abdominal discomfort and uptake of albuminaemia has sometimes, perhaps erroneously (see below), been used to diagnose malnutrition [10]. glucose may also contribute to what we define as malnourishment in CRF. These may exert their action either by direct nutrient loss or by triggering the Protein and energy requirements in chronic renal inflammatory response. However, since malnutrition failure also occurs in pre-dialysis patients [7], it is evident that dialysis-unrelated factors, e.g. infectious and The protein requirements in maintenance dialysis inflammatory complications as well as co-morbidity, patients are not well defined. It can be assumed that may also be important contributors to malnutrition the variation in protein requirements is much greater in CRF. among dialysis patients than in healthy subjects, due to additional causes of variation, such as endocrine Correspondence and offprint requests to: Peter Stenvinkel, MD, and biochemical abnormalities, anaemia, drugs, physDepartment of Renal Medicine, K56, Huddinge University Hospital, S-141 86 Huddinge, Sweden. ical inactivity and co-morbid conditions, e.g. cardiovas-

Potent and nontoxic antisense oligonucleotides containing locked nucleic acids

Abstract: Insufficient efficacy and/or specificity of antisense oligonucleotides limit their in vivo usefulness. We demonstrate here that a high-affinity DNA analog, locked nucleic acid (LNA), confers several desired properties to antisense agents. Unlike DNA, LNA/DNA copolymers were not degraded readily in blood serum and cell extracts. However, like DNA, the LNA/DNA copolymers were capable of activating RNase H, an important antisense mechanism of action. In contrast to phosphorothioate-containing oligonucleotides, isosequential LNA analogs did not cause detectable toxic reactions in rat brain. LNA/DNA copolymers exhibited potent antisense activity on assay systems as disparate as a G-protein-coupled receptor in living rat brain and an Escherichia coli reporter gene. LNA-containing oligonucleotides will likely be useful for many antisense applications.

Infections as a major preventable cause of human cancer

Abstract: Infections may be responsible for over 15% of all malignancies worldwide. Important mechanisms by which infectious agents may induce carcinogenesis include the production of chronic inflammation, the transformation of cells by insertion of oncogenes and inhibition of tumour suppressors, and the induction of immunosuppression. Common characteristics shared by infectious agents linked to malignancies are that they are persistent in the host, often highly prevalent in the host population and induce cancer after a long latency. The associations between a selection of infectious agents and malignancies are covered in detail.

Docosahexaenoic Acid, a Ligand for the Retinoid X Receptor in Mouse Brain

Abstract: The retinoid X receptor (RXR) is a nuclear receptor that functions as a ligand-activated transcription factor. Little is known about the ligands that activate RXR in vivo. Here, we identified a factor in brain tissue from adult mice that activates RXR in cell-based assays. Purification and analysis of the factor by mass spectrometry revealed that it is docosahexaenoic acid (DHA), a long-chain polyunsaturated fatty acid that is highly enriched in the adult mammalian brain. Previous work has shown that DHA is essential for brain maturation, and deficiency of DHA in both rodents and humans leads to impaired spatial learning and other abnormalities. These data suggest that DHA may influence neural function through activation of an RXR signaling pathway.

A pooled analysis of magnetic fields and childhood leukaemia.

Abstract: Previous studies have suggested an association between exposure to 50–60 Hz magnetic fields (EMF) and childhood leukaemia. We conducted a pooled analysis based on individual records from nine studies, including the most recent ones. Studies with 24/48-hour magnetic field measurements or calculated magnetic fields were included. We specified which data analyses we planned to do and how to do them before we commenced the work. The use of individual records allowed us to use the same exposure definitions, and the large numbers of subjects enabled more precise estimation of risks at high exposure levels. For the 3203 children with leukaemia and 10 338 control children with estimated residential magnetic field exposures levels < 0.4 μT, we observed risk estimates near the no effect level, while for the 44 children with leukaemia and 62 control children with estimated residential magnetic field exposures ≥ 0.4 μT the estimated summary relative risk was 2.00 (1.27–3.13), P value = 0.002). Adjustment for potential confounding variables did not appreciably change the results. For North American subjects whose residences were in the highest wire code category, the estimated summary relative risk was 1.24 (0.82–1.87). Thus, we found no evidence in the combined data for the existence of the so-called wire-code paradox. In summary, the 99.2% of children residing in homes with exposure levels < 0.4 μT had estimates compatible with no increased risk, while the 0.8% of children with exposures ≥ 0.4 μT had a relative risk estimate of approximately 2, which is unlikely to be due to random variability. The explanation for the elevated risk is unknown, but selection bias may have accounted for some of the increase. © 2000 Cancer Research Campaign

Efficient presentation of exogenous antigen by liver endothelial cells to CD8+ T cells results in antigen-specific T-cell tolerance.

Abstract: Myeloid antigen-presenting cells (APC) are known to cross-present exogenous antigen on major histocompatibility class I molecules to CD8+ T cells and thereby induce protective immunity against infecting microorganisms. Here we report that liver sinusoidal endothelial cells (LSEC) are organ-resident, non-myeloid APC capable of cross-presenting soluble exogenous antigen to CD8+ T cells. Though LSEC employ similar molecular mechanisms for cross-presentation as dendritic cells, the outcome of cross-presentation by LSEC is CD8+ T cell tolerance rather than immunity. As uptake of circulating antigens into LSEC occurs efficiently in vivo, it is likely that cross-presentation by LSEC contributes to CD8+ T cell tolerance observed in situations where soluble antigen is present in the circulation.

Psychopathy and the predictive validity of the PCL-R: an international perspective

Abstract: Its controversial past notwithstanding, psychopathy has emerged as one of the most important clinical constructs in the criminal justice and mental health systems. One reason for the surge in theoretical and applied interest in the disorder is the development and widespread adoption of reliable and valid methods for its measurement. The Hare PCL-R provides researchers and clinicians with a common metric for the assessment of psychopathy, and has led to a surge in replicable and meaningful findings relevant to the issue of risk for recidivism and violence, among other things. Most of the research thus far has been based on North American samples of offenders and forensic psychiatric patients. We summarize this research and compare it with findings from several other countries, including England and Sweden. We conclude that the ability of the PCL-R to predict recidivism, violence, and treatment outcome has considerable cross-cultural generalizability, and that the PCL-R and its derivatives play a major role in the understanding and prediction of crime and violence.

Alignment of Biological Macromolecules in Novel Nonionic Liquid Crystalline Media for NMR Experiments

Abstract: n-Alkyl-poly(ethylene glycol)/n-alkyl alcohol and glucopone/n-hexanol mixtures are shown to form dilute liquid crystalline phases in aqueous solution which are suitable for partial alignment of biological macromolecules in a magnetic field. The constituent compounds are commercially available and inexpensive. The poly(ethylene glycol)-based systems are uncharged and thus insensitive with respect to pH, little sensitive with respect to salt, and tolerant against high protein concentrations. They are demonstrated to be suitable for measurements of residual dipolar couplings in proteins, DNA, and a protein/DNA complex. The stability range of the lamellar phase with respect to temperature was explored for different mixtures and guidelines are provided for the use of these lyotropic systems in NMR spectroscopy.

Short-lived green fluorescent proteins for quantifying ubiquitin/proteasome-dependent proteolysis in living cells

Abstract: The ubiquitin/proteasome-dependent proteolytic pathway is an attractive target for therapeutics because of its critical involvement in cell cycle progression and antigen presentation. However, dissection of the pathway and development of modulators are hampered by the complexity of the system and the lack of easily detectable authentic substrates. We have developed a convenient reporter system by producing N-end rule and ubiquitin fusion degradation (UFD)-targeted green fluorescent proteins that allow quantification of ubiquitin/proteasome-dependent proteolysis in living cells. Accumulation of these reporters serves as an early predictor of G2/M arrest and apoptosis in cells treated with proteasome inhibitors. Comparison of reporter accumulation and cleavage of fluorogenic substrates demonstrates that the rate-limiting chymotrypsin-like activity of the proteasome can be substantially curtailed without significant effect on ubiquitin-dependent proteolysis. These reporters provide a new powerful tool for elucidation of the ubiquitin/proteasome pathway and for high throughput screening of compounds that selectively modify proteolysis in vivo.

Marital Stress Worsens Prognosis in Women With Coronary Heart Disease: The Stockholm Female Coronary Risk Study

Abstract: ContextPsychosocial stress has been associated with incidence of coronary heart disease (CHD) in men, but the prognostic impact of such stress rarely has been studied in women.ObjectiveTo investigate the prognostic impact of psychosocial work stress and marital stress among women with CHD.Design and SettingPopulation-based, prospective follow-up study conducted in the city of Stockholm, Sweden.ParticipantsA total of 292 consecutive female patients aged 30 to 65 years (n = 279 working or cohabiting with a male partner) who were hospitalized for acute myocardial infarction or unstable angina pectoris between February 1991 and February 1994. Patients were followed up from the date of clinical examination until August 1997 (median, 4.8 years).Main Outcome MeasuresRecurrent coronary events, including cardiac death, acute myocardial infarction, and revascularization procedures, by marital stress (assessed using the Stockholm Marital Stress Scale, a structured interview) and by work stress (assessed using the ratio of work demand to work control).ResultsAmong women who were married or cohabiting with a male partner (n = 187), marital stress was associated with a 2.9-fold (95% confidence interval [CI], 1.3-6.5) increased risk of recurrent events after adjustment for age, estrogen status, education level, smoking, diagnosis at index event, diabetes mellitus, systolic blood pressure, smoking, triglyceride level, high-density lipoprotein cholesterol level, and left ventricular dysfunction. Among working women (n = 200), work stress did not significantly predict recurrent coronary events (hazard ratio, 1.6; 95% CI, 0.8-3.3).ConclusionsOur results indicate that marital stress but not work stress predicts poor prognosis in women aged 30 to 65 years with CHD. These findings differ from previous findings in men and suggest that specific preventive measures be tailored to the needs of women with CHD.

Risk factors for surgery and postoperative recurrence in Crohn's disease.

Abstract: Patients with Crohn’s disease (CD) are a heterogeneous group and consequently the individual course of the disease is difficult to predict: some have a rather mild form, but others suffer frequent flare-ups requiring resection, with symptoms recurring soon after surgery. In accordance with the chronic nature of the disease, only 12% of patients with CD have been reported to have experienced a relapse-free course 10 years after diagnosis. 1 To preserve bowel function, a more conservative surgical approach has been adopted during the past few decades. In cases of medical intractabilty, internal fistulas, intestinal obstruction, hemorrhage, toxic dilatation, or acute perforation, however, surgical resection inevitably becomes necessary. 2 Despite the general knowledge of a high probability of intestinal resections in CD patients, few studies since the initial work in the 1970s and 1980s 3 have focused on the risk and risk factors for the initial intestinal resection in CD. 4,5 In contrast, several studies have evaluated the risk and possible risk factors for postoperative recurrent disease, 6,7 but these studies have produced disparate results. 5,8,9 Age, gender, disease localization, preoperative duration of history, and the presence of granulomas have all had different impacts on postoperative recurrence, and thus no sure risk factor, apart from smoking, 10 has yet been established. The varying results may have been mainly attributable to different study designs with reference to the type of patients included and the definition of recurrence. The aims of this study were to evaluate the probability of undergoing intestinal resection and to assess the risk of postoperative recurrence in a population-based cohort. Included in the assessment were the impact of gender, age, and disease localization at diagnosis, perianal fistulas, duration of disease, and time trends during a 35-year period.

Structure and function of adenosine receptors and their genes

Abstract: Four adenosine receptors have been cloned from many mammalian and some non-mammalian species In each case the translated part of the receptor is encoded by two separate exons Two separate promoters regulate the A1 receptor expression, and a similar situation may pertain also for the other receptors The receptors are expressed in a cell and tissue specific manner, even though A1 and A2B receptors are found in many different cell types Emerging data indicate that the receptor protein is targeted to specific parts of the cell A1 and A3 receptors activate the Gi family of G proteins, whereas A2A and A2B receptors activate the Gs family However, other G proteins can also be activated even though the physiological significance of this is unknown Following the activation of G proteins several cellular effector pathways can be affected Signaling via adenosine receptors is also known to interact in functionally important ways with signaling initiated via other receptors

Transfer of CD4+ T Cells Aggravates Atherosclerosis in Immunodeficient Apolipoprotein E Knockout Mice

Abstract: Background—Atherosclerosis is associated with immune responses to oxidized lipoproteins and certain microorganisms, but the role of specific immunity has remained unclear. Methods and Results—To study the role of immunity in atherosclerosis, we crossed atherosclerosis-prone apoE—/– mice with immunodeficient scid/scid mice. The offspring showed a 73% reduction in aortic fatty streak lesions when compared with immunocompetent apoE–/– mice. Transfer of CD4+ T cells from apoE–/– to immunodeficient apoE–/–/scid/scid mice increased lesions by 164%. This was associated with the infiltration of transferred T cells into lesions, increased circulating interferon-γ levels, and increased I-A expression in lesions. Conclusions—CD4+ T cells carry disease-promoting immunity in atherosclerosis.