CD19-positive antibody-secreting cells provide immune memory.

Long-lived antibody-secreting cells (ASCs) are critical for the maintenance of humoral immunity through the continued production of antibodies specific for previously encountered pathogen or vaccine antigens. Recent reports describing humoral immune memory have suggested the importance of long-lived CD19- bone marrow (BM) ASCs, which secrete antibodies recognizing previously encountered vaccine antigens. However, these reports do not agree upon the unique contribution of the CD19+ BM ASC subset toward humoral immunity. Here, we found both CD19+ and negative ASCs from human BM were similar in functional capacity to react to a number of vaccine antigens via ELISpot assays. The CD19+ cells were the predominant ASC population found in lymphoid tissues, and unlike the CD19- ASCs, which were found only in spleen and BM, the CD19+ ASCs were found in tonsil and blood. CD19+ ASCs from the BM, spleen, and tonsil were capable of recognizing polio vaccine antigens, indicating the CD19+ ASC cells play a novel role in long-lasting immune defense. Comparative gene expression analysis indicated CD19+ and negative BM ASCs differed significantly by only 14 distinct messenger RNAs and exhibited similar gene expression for cell cycle, autophagy, and apoptosis control necessary for long life. In addition, we show identical CDR-H3 sequences found on both BM ASC subsets, indicating a shared developmental path. Together, these results provide novel insight for the distribution, function, genetic regulation, and development of long-lived ASCs and may not only impact improved cell therapies but also enhance strategies for vaccine development.

Early adopters of perioperative medicine: who are they and what motivates them?

Perioperative medicine is an emerging specialty aimed at improving outcomes in the high-risk surgical population. The authors set out to characterize the demographics and determine the motivation of 'early adopters' of this specialty by retrospectively reviewing the application forms of students enrolled on the UCL Perioperative Medicine Masters Programme. A total of 139 applications were reviewed. The median age of applicants was 35 years; 81% were UK based, with the remainder from a worldwide distribution. Seventeen per cent were consultant anaesthetists and 64% anaesthetic trainees, with the remainder including doctors from other specialties (17%) and nurses (2%). Qualitative analysis using grounded theory methodology revealed common motivational themes: the belief that perioperative medicine would lead to better patient care, that it represents the future working practice for anaesthetists, a desire to be able to better lead local developments, and personal fulfilment and benefit. The responses provided insight into the motivation of an international cohort of professionals. Perioperative medicine was perceived as a developing multidisciplinary specialty that will lead to better patient care. Applicants understood the importance of perioperative care extending beyond the operating theatre which may explain the growing demand for training in perioperative medicine.

Use of CT in the management of anterior cruciate ligament revision surgery.

Anterior cruciate ligament (ACL) injuries occur most commonly in individuals between 18 and 29 years of age and are strongly correlated with sporting activity, with female athletes being at higher risk of ACL rupture than their male counterparts. ACL reconstruction is one of the most frequently performed procedures in orthopaedic surgery, having a reported incidence of 85 per 100,000 head of population in the at-risk age group. Subsequent graft failure is most commonly caused by recurrent trauma, followed by tunnel malpositioning, although the choice of graft type does not appear to affect outcome. The Danish ACL registry reported that ACL revisions accounted for 7.5% of all ACL reconstruction surgery performed between 2005 and 2008. Revision of ACL reconstruction is recognized to carry a worse outcome than primary reconstruction. Preoperative imaging has become a crucial part of surgical planning in these patients, with great reliance placed on computed tomography (CT). The radiologist should be able to recognize the types of primary repair and must be able to assess for the complications of primary surgery, such as tunnel malpositioning, tunnel widening, and fixation device failure. Revision is commonly a two-stage procedure with bone grafting of the tunnels prior to the definitive ligament repair. The radiologist should be able to asses for adequate bone graft incorporation. The purpose of this article is to present a review of the use of CT in the management of ACL revision surgery with examples of commonly used fixation devices; complications, such as tunnel widening and tunnel malpositioning; and bone graft incorporation.

Design and cohort description of the InterAct Project: an examination of the interaction of genetic and lifestyle factors on the incidence of type 2 diabetes in the EPIC Study.

AIMS/HYPOTHESIS: Studying gene-lifestyle interaction may help to identify lifestyle factors that modify genetic susceptibility and uncover genetic loci exerting important subgroup effects. Adequately powered studies with prospective, unbiased, standardised assessment of key behavioural factors for gene-lifestyle studies are lacking. This case-cohort study aims to investigate how genetic and potentially modifiable lifestyle and behavioural factors, particularly diet and physical activity, interact in their influence on the risk of developing type 2 diabetes. METHODS: Incident cases of type 2 diabetes occurring in European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts between 1991 and 2007 from eight of the ten EPIC countries were ascertained and verified. Prentice-weighted Cox regression and random-effects meta-analyses were used to investigate differences in diabetes incidence by age and sex. RESULTS: A total of 12,403 verified incident cases of type 2 diabetes occurred during 3.99 million person-years of follow-up of 340,234 EPIC participants eligible for InterAct. We defined a centre-stratified subcohort of 16,154 individuals for comparative analyses. Individuals with incident diabetes who were randomly selected into the subcohort (n = 778) were included as cases in the analyses. All prevalent diabetes cases were excluded from the study. InterAct cases were followed-up for an average of 6.9 years; 49.7% were men. Mean baseline age and age at diagnosis were 55.6 and 62.5 years, mean BMI and waist circumference values were 29.4 kg/m(2) and 102.7 cm in men, and 30.1 kg/m(2) and 92.8 cm in women, respectively. Risk of type 2 diabetes increased linearly with age, with an overall HR of 1.56 (95% CI 1.48-1.64) for a 10 year age difference, adjusted for sex. A male excess in the risk of incident diabetes was consistently observed across all countries, with a pooled HR of 1.51 (95% CI 1.39-1.64), adjusted for age. CONCLUSIONS/INTERPRETATION: InterAct is a large, well-powered, prospective study that will inform our understanding of the interplay between genes and lifestyle factors on the risk of type 2 diabetes development.

Myositis ossificans as a complication of hamstring autograft harvest for open primary anterior and posterior cruciate ligament and posterolateral corner reconstruction.

Post-traumatic myositis ossificans is a benign condition of heterotopic ossification of unknown aetiology which typically is related to trauma from a single blow or repeated episodes of microtrauma. A case of myositis ossificans that developed after hamstring autograft harvest for an open cruciate ligament and posterolateral corner reconstruction is described, a previously unrecognised complication of this procedure.

Clinical and ultrasound examination of the leeds enthesitis index in psoriatic arthritis and rheumatoid arthritis.

Objective. To compare scores for the Leeds enthesitis index in psoriatic arthritis and rheumatoid arthritis using clinical assessment and ultrasonography (US). Design. Swelling and tenderness of the enthesis was assessed at six sites: lateral epicondyles of humerus (LE), medial condyles of femur (MC), and the insertion of the Achilles tendon (AT). US assessed "inflammatory activity" (power Doppler signal, oedema, tendon thickening, and bursal swelling) and "damage" (erosions and enthesophytes). Results. 94 patients were included, 71 with PsA and 23 with RA. The patients with RA were significantly older (PsA 47.6 years; RA 62.6 years; (mean difference in ages =15.0 years, 95% CI 9.3-20.7 years)). US scores were higher in RA at the LE, significantly so for the "damage" scores. No differences between RA and PsA were seen at the other sites. As a result, the odds ratio for PsA, given an US score above the median, was 0.41 (0.13-1.03). However, using the clinical score, the odds ratio for PsA was 2.16 (0.81-5.70). Conclusions. Although clinical scores of enthesitis are greater in PsA compared to RA, US enthesitis scores did not distinguish between RA and PsA. This may in part be due to more frequent juxta-articular involvement in RA and in part due to the older age of the subjects with RA.

Association of variants in the fat mass and obesity associated (FTO) gene with polycystic ovary syndrome.

AIMS/HYPOTHESIS: Variants in the fat-mass and obesity-associated gene (FTO) influence susceptibility to type 2 diabetes via an effect on adiposity/obesity. Given the important role of obesity in the aetiology of both polycystic ovary syndrome (PCOS) and type 2 diabetes mellitus, our aim was to establish whether FTO variants are also implicated in PCOS susceptibility. METHODS: We performed a genetic association study of FTO variant rs9939609 using case-control analyses, conducted in 463 PCOS patients (geometric mean BMI 27.5 kg/m(2)) and 1,336 female controls (geometric mean BMI 25.3 kg/m(2)) of UK British/Irish origin. We also sought evidence for associations between FTO variation and circulating testosterone levels in 324 UK PCOS patients and 1,000 women from the Northern Finland Birth Cohort of 1966. Outcome measures included FTO rs9939609 genotype frequencies by participant group and androgen measures (testosterone, free androgen index) by genotype. RESULTS: There was a significant association between FTO genotype and PCOS status in the UK case-control analysis, which was attenuated by adjustment for BMI (Cochran-Armitage test, odds ratio [per minor allele copy] 1.30 [95% CI 1.12, 1.51], p = 7.2 x 10(-4) [unadjusted], p = 2.9 x 10(-3) [adjusted]). This association was most evident in obese PCOS patients (PCOS patients below median BMI vs UK controls, p = 0.11; above median BMI vs controls, p = 2.9 x 10(-4)). No relationship between FTO genotype and androgen levels was seen. CONCLUSIONS/INTERPRETATION: We provide the first evidence that variants that predispose to common obesity also result in altered susceptibility to PCOS, confirming the mechanistic link between these conditions. The predominant effect of FTO variants on PCOS susceptibility is probably mediated through adiposity.

Disparate genetic influences on polycystic ovary syndrome (PCOS) and type 2 diabetes revealed by a lack of association between common variants within the TCF7L2 gene and PCOS.

AIMS/HYPOTHESIS: Common variants of the gene encoding transcription factor 7-like 2 (TCF7L2) have a powerful effect on individual risk of type 2 diabetes (per allele odds ratio approximately 1.35). Polycystic ovary syndrome (PCOS) and type 2 diabetes are familial conditions sharing common features. Based on this, the aim of the present study was to establish whether variation in TCF7L2 also influences the development of PCOS. METHODS: We conducted a genetic association study of variants of TCF7L2 (rs7903146 and rs12255372) using both case-control and quantitative trait approaches. Case-control analyses were conducted in (1) 369 PCOS cases and 2574 controls of UK British/Irish origin, and (2) 540 women with PCOS symptoms and 1083 controls from the Northern Finland Birth Cohort of 1966. Quantitative trait analyses (androgen levels) were also performed (1249 individuals). RESULTS: There was no association between rs7903146 and PCOS in the UK case-control study (Cochran-Armitage test, p = 0.51); nor with symptomatic status in the Finnish cohort (p = 0.36). In addition, there were no relationships between the TCF7L2 single nucleotide polymorphism rs7903146 and androgen levels (UK cases, p = 0.99; Finnish controls, p = 0.57; Finnish symptomatic cases, p = 0.80). Results at rs12255372 were similar, reflecting strong linkage disequilibrium with rs7903146. CONCLUSIONS/INTERPRETATION: Our study was powered to detect an effect on PCOS susceptibility similar to that previously reported for these variants on type 2 diabetes. Failure to detect any evident association with PCOS provides the strongest evidence yet that the genetic architecture of these related conditions is qualitatively distinct.

Calcific tendonitis of the quadriceps.

The case reported is of a 46 year old male who presented with a history of acute on chronic knee pain. The clinical features and investigations suggested a tear of the quadriceps tendon, with pre-existing chronic calcific enthesopathy. The operative findings were of an acute collection of calcific material within the quadriceps tendon. This acute presentation and calcific collection have not previously been reported in the quadriceps tendon.

Pre-pouch ileitis: a disease of the ileum in ulcerative colitis after restorative proctocolectomy.

OBJECTIVE: Ileal inflammation in ulcerative colitis can occur as backwash ileitis or prestomal ileitis. After restorative proctocolectomy (RPC), ileal inflammation may be present in the pouch (pouchitis) but inflammation proximal to the pouch in the neo-terminal ileum, so called pre-pouch ileitis (PI), has also been observed. As pouchitis is increasingly common and PI can mimic it, our aim was to characterize this condition. SUBJECTS AND METHODS: A review of prospectively collected data on 571 inflammatory bowel disease patients undergoing follow-up after RPC in a single centre over 22 years was performed. The histology of biopsy material was reviewed and staining for colonic mucosal phenotypic changes was undertaken. It was not routine practice to prospectively assess all patients for pre-pouch ileitis when the database was constructed. RESULTS: Of 19 patients with inflammation of the pre-pouch neo-terminal ileum (NTI) identified three had Crohn's disease and one a NSAID stricture. The remaining 15 had a characteristic diffuse inflammation extending from the NTI-pouch junction proximally: pre-pouch ileitis. The inflammation extended proximally for up to 50 cm. Fistula formation was seen in only one. Seven (47%) of 15 had pouchitis but only two had suffered backwash ileitis pre-operatively. Seven responded to medical therapy and four to surgery. The histological appearances including staining for colonic phenotypic change were similar in PI and pouchitis. CONCLUSION: Pre-pouch ileitis is uncommon. As the patients' previous diagnosis of UC was confirmed and there was no radiological or histological evidence of Crohn's disease, PI appears to have a distinct pathogenesis from Crohn's disease.

Large-scale studies of the association between variation at the TNF/LTA locus and susceptibility to type 2 diabetes.

AIMS/HYPOTHESIS: The proinflammatory cytokine TNF-alpha has been implicated in the pathogenesis of insulin resistance and type 2 diabetes, and variation in the gene encoding TNF-alpha (TNF) has shown inconsistent associations with susceptibility to both conditions. Additionally, the coding non-synonymous variant T60N in the neighbouring LTA gene has been reported to be associated with type 2 diabetes. The present study aimed to obtain a robust assessment of the role of variation in the tightly linked TNF/LTA region in diabetes susceptibility by genotyping TNF and LTA variants in large case-control resources. MATERIALS AND METHODS: The G-308A and G-238A TNF promoter variants and the LTA T60N polymorphism were genotyped in two UK case samples that were ascertained for positive family history and/or early onset of type 2 diabetes (combined n=858) and in 1,257 ethnically matched controls. RESULTS: There were no significant associations between the T60N, G-308A or G-238A genotype and type 2 diabetes in the combined analysis (exact Cochran-Mantel-Haenszel statistic for ordered genotypes for T60N, p=0.69; for G-308A, p=0.51; for G-238A, p=0.16). CONCLUSIONS/INTERPRETATION: The present study, one of the largest association analyses yet reported at this locus, provides no evidence that the specific TNF or LTA variants examined influence susceptibility to type 2 diabetes. More comprehensive studies of the TNF/LTA locus in substantially larger sample sets are required to establish whether genome sequence variation at this locus truly influences susceptibility to type 2 diabetes.

Pylorus-preserving pancreaticoduodenectomy for advanced duodenal disease in familial adenomatous polyposis.

BACKGROUND: Although only 5 per cent of patients with familial adenomatous polyposis (FAP) die from duodenal cancer, a recent study indicated that the mortality rate is much higher in patients with Spigelman stage IV disease. This has prompted an increased rate of referral for excisional surgery and an analysis of the results. METHODS: Between January 1994 and June 2002, 16 patients with FAP (mean age 55 years; eight men) were referred to a single surgeon for pylorus-preserving pancreaticoduodenal resection for Spigelman stage IV duodenal adenomatosis. RESULTS: One patient died from multiple organ failure after relaparotomy for haemorrhage and a jejunal perforation; other major complications included anastomotic leak (one), primary haemorrhage (one), lymphatic leak (one), chylous ascites (one), pulmonary embolus (two) and prolonged delayed gastric emptying that required total parenteral nutrition (three). Overall there were 11 major complications in eight patients. Two patients developed insulin-dependent diabetes and one postprandial dumping. Postoperative histological examination revealed five unsuspected cancers, which led to four deaths within 3 years of surgery. One patient died 2 months after surgery from pulmonary thromboembolism and another at 5 months from an inoperable brain tumour. Nine of the 16 patients were alive and well at a mean of 38 months after surgery. CONCLUSION: The choice between continued endoscopic surveillance and excisional surgery for Spigelman stage IV duodenal disease remains finely balanced.

[Imaging of bacterial infections of the sacroiliac joint]. / Darstellung bakterieller Infektionen im Sakroiliakalgelenk.

Infection of the sacroiliac joint can be pyogenic or granulomatous and is usually unilateral. There are a number of predisposing conditions including drug abuse and intra articular steroid injection, but in 44% of cases, no definite predisposing factors can be identified. Considerable delay between presentation and diagnosis is recognized. The clinical picture may be non-specific and variable, and clinical suspicion may be low due to the relatively low incidence of the condition. This is compounded by difficulties in clinical examination of the SUs. The diagnosis is based on a history suggestive of infection, clinical or radiographic localization to the SUs, and a positive blood culture or joint aspirate. The pathology of pyogenic sacroiliitis is reviewed with respect to the anatomy of the SU, and the differential diagnoses considered. The imaging findings, and relative merits of all the modalities are discussed with particular consideration given to changes over the course of the disease. Imaging strategies are evaluated and proposed. As the commonest presenting symptom is low back pain, consideration should be given to the addition of a STIR sequence covering the SUs on all routine lumbar spine MR examinations. MR imaging is the most sensitive and specific imaging modality, while CT-guided arthrocentesis improves diagnostic confidence. Tc99MDP blood pool imaging mirrors the clinical features of resolution, and scintigraphy may be the best method to monitor response to treatment. Targeted antibiotic therapy usually leads to a full recovery. A high incidence of clinical suspicion, with MR imaging at an early stage are the essential prerequisites to an accurate diagnosis of bacterial sacroiliitis.

Duodenal cancer in patients with familial adenomatous polyposis (FAP): results of a 10 year prospective study.

BACKGROUND: Duodenal cancer is one of the leading causes of death in familial adenomatous polyposis (FAP) patients. An endoscopic surveillance programme was therefore initiated in 1988, the outcome of which is described in this paper. METHODS: We report the 10 year follow up of 114 patients with FAP who were prospectively screened for the presence and severity of duodenal adenomas. RESULTS: Six of 114 patients (median age 67 years) developed duodenal adenocarcinoma. Four of these were from 11 patients who originally had Spigelman stage IV disease (advanced duodenal polyposis), which gives a 36% risk within this group of developing cancer. One case of duodenal cancer arose from 41 patients who originally had stage III disease (2%) and one cancer arose from 44 patients with original stage II disease (2%). All six patients have died: five were inoperable and one had recurrence three years after a pancreaticoduodenectomy. There was no association between duodenal cancer and site of germline mutation of the APC gene. CONCLUSIONS: Surveillance for duodenal adenocarcinoma and subsequent early referral for curative surgery has not been effective. Selection of patients with advanced but benign (Spigelman stage IV) duodenal polyposis for prophylactic pancreaticoduodenectomy should therefore be considered and can now be justified on the basis of these results. More comprehensive endoscopic surveillance of high risk (stage III and IV) patients is needed in an attempt to avoid underestimating the severity of duodenal polyposis, and to evaluate the role of endoscopic therapy in preventing advanced disease.

A cluster of fulminant myocarditis cases in children, Baltimore, Maryland, 1997.

The true incidence of myocarditis in children is difficult to estimate because many mild cases go undetected. This study describes an unusual cluster of myocarditis cases that occurred in young children living in the greater Baltimore area between May and October 1997. A search of multiple comprehensive databases and interviews with area pediatric cardiologists were conducted to identify unreported cases and determine the background rate of myocarditis in the area. Seven cases of myocarditis were found as well as two with a similar clinical picture and myocardial fibrosis on tissue examination. Six case patients with active myocarditis and one child with fibrosis died. The case children were predominantly black (eight of nine) and male (seven of nine), with no identifiable risk factors. The disease was characterized by a fulminant course with malignant arrhythmias. The greatest number of pediatric myocarditis deaths reported in 1 year prior to 1997 was three. Myocardial tissues were examined using immunohistochemistry, in situ hybridization, and polymerase chain reaction but no etiologic agent was identified. This outbreak is unusual because of both the number of cases and the fulminant course of the disease in this group of children.

Cluster of serogroup C meningococcal disease associated with attendance at a party.

BACKGROUND: An unexplained increase has occurred in the incidence of invasive meningococcal disease in adolescents and young adults. METHODS: We investigated a cluster of serogroup C meningococcal disease in 3 previously healthy young adults who had attended a party in Maryland. Molecular subtyping was done on the isolates from the 3 cluster cases and 4 control isolates by pulsed-field gel electrophoresis (PFGE). The only common exposure was attendance at the party, where a large number of people reportedly smoked tobacco or marijuana and/or drank alcohol. RESULTS: The PFGE analysis of the 3 case isolates showed identical molecular subtypes. CONCLUSION: This investigation strongly suggests that transmission of the cluster strain occurred at the party. Transmission may have occurred in part as a result of the recently described risk factors of binge drinking and smoking. Taken together, these findings suggest that some of the recent increase in invasive meningococcal disease may be due to modifiable risk factors.

Chlorotrifluoroethylcysteine interaction with rabbit proximal tubule cell basolateral membrane organic anion transport and apical membrane amino acid transport.

The interaction of the cysteine conjugate S-(1-chloro-1,2,2, -trifluoroethyl)-L-cysteine (CTFC) with organic anion and amino acid transport in the basolateral and apical membranes was examined with rabbit renal proximal tubule suspensions and primary cultures of rabbit renal proximal tubule cells. The apparent K(i) for CTFC inhibition of the 1-min uptake of [(3)H]p-aminohippurate in tubule suspensions was 105+/-3 microM and suggests that CTFC interacts with basolateral organic anion transport. Also, the addition of 1 mM CTFC decreased the secretion and intracellular accumulation of fluorescein by approximately 70 to 75%. The addition of 1 mM CTFC to the apical compartment decreased the reabsorption and intracellular accumulation of the amino acid [(3)H]phenylalanine by approximately 60 to 70%. Similar to CTFC, saturating concentrations of the organic anion [(3)H]p-aminohippurate and the amino acid phenylalanine reduced by approximately 75% fluorescein secretion and [(3)H]phenylalanine reabsorption, respectively, by approximately 60 to 70%. Thus, the cysteine conjugate CTFC appears to be a potent inhibitor of basolateral organic anion and apical amino acid transepithelial transport. In contrast to its effects on apical phenylalanine uptake, CTFC had no effect on the basal uptake of [(3)H]phenylalanine by primary cultures. The presence of CTFC in the external bath did trans-stimulate the efflux of fluorescein and [(3)H]phenylalanine across the basal and apical membrane in tubule suspensions or primary cultures, respectively, grown on plastic. Collectively, these data demonstrate that CTFC interacts with, and is transported by, two anatomically and functionally distinct transporters, the basolateral organic anion and apical neutral amino acid pathways, in the rabbit renal proximal tubule cell.

Relation of cysteine conjugate nephrotoxicity to transport by the basolateral organic anion transport system in isolated S2 segments of rabbit proximal renal tubules.

We examined basolateral transport of the radiolabeled zwitterionic nephrotoxic cysteine S-conjugate, S-(1,2-dichlorovinyl)-L-cysteine (DCVC), inhibition of such transport and the effects of inhibition of transport on the toxicity produced by DCVC in isolated S2 segments of rabbit proximal tubules. High concentrations of unlabeled DCVC itself and an unlabeled nontoxic cysteine S-conjugate, S-(2-benzothiazole)-L-cysteine cis-inhibited the basolateral uptake of radiolabeled DCVC by approximately 80 to 85%. High concentrations of para-aminohippurate, the prototype substrate for the basolateral organic anion transport system, and probenecid, a well-known inhibitor of basolateral organic anion transport, cis-inhibited the basolateral uptake of radiolabeled DCVC by approximately 70%, whereas a high concentration of L-phenylalanine had little effect. High concentrations of S-(2-benzothiazole)-L-cysteine and para-aminohippurate in the bathing medium with DCVC inhibited the loss of 86Rb (used as a K+ surrogate to measure toxicity) from S2 segments produced by DCVC alone to approximately the same extent as they inhibited uptake of DCVC. Under the same circumstances, probenecid completely inhibited 86Rb loss. These data indicate that in rabbit proximal renal S2 tubules basolateral entry of DCVC can occur to a major extent via the organic anion transport pathway and that inhibition of such entry can reduce toxicity to approximately the same extent that entry is reduced. They also suggest that probenecid provides additional protection from DCVC toxicity.

Constitutive expression of costimulatory molecules by human microglia and its relevance to CNS autoimmunity.

Human microglia constitute the primary residential antigen presenting cells (APCs) in the central nervous system (CNS) and have the capacity of activating myelin reactive T-cells. T-cell activation requires two signals: first is the interaction of the T-cell receptor with the MHC-antigen complex and, secondly, contact of the CD28/CTLA4 T-cell surface molecules with the B7 family of costimulatory molecules on the APCs. We have previously shown high expression of B7.1 in early multiple sclerosis (MS) plaques, suggesting that acute T-cell-mediated CNS inflammation may require local B7.1 upregulation. We have now examined the expression of B7.1 and B7.2 costimulatory molecules on resting ex-vivo human microglia isolated directly from biopsy specimens. We found constitutive expression of B7.2 but not B7.1 on resting microglia, suggesting that B7.2 expression may lead to downregulation of pro-inflammatory Th1 T-cell responses in the normal brain.