[Thrombosis with Thrombocytopenia Syndrome after ChAdOx1 nCoV-19 vaccination].

A 48-year-old Japanese man who had no previous medical history received his first dose of the ChAdOx1 nCoV-19 vaccine. Ten days after the vaccine administration, he developed a headache. Laboratory results indicated throm-bocytopenia and DIC. A head CT revealed microbleeding in the left parietal lobe. Contrast-enhanced CT showed thrombus in the left transverse sinus and left sigmoid sinus. A brain MRI demonstrated venous hemorrhagic infarction and subarachnoid hemorrhages in the left parietal lobe, and whole-body enhanced CT also revealed portal vein embolism and renal infarction. He was diagnosed with thrombosis with thrombocytopenia syndrome, and was treated according to the guideline. He has been recovering with the treatments. This is the first reported case of TTS associated with the ChAdOx1 nCoV-19 vaccine in Japan.

Hemichorea after hypoglycemic episodes with negative MRI findings in an elderly woman with poorly controlled type 2 diabetes mellitus: a case report.

BACKGROUND: Diabetic chorea appears during the course of poorly-controlled diabetes. While chorea associated with diabetes mellitus usually occurs during hyperglycemic episodes, hypoglycemia can also cause diabetic chorea. Brain magnetic resonance imaging (MRI) is useful for evaluating the pathogenesis of diabetic chorea. However, several diabetic chorea cases have reportedly not shown abnormal high-intensity in the putamen and striatum on T1-weighted images. CASE PRESENTATION: We report a 74-year-old woman who was admitted to our hospital for treatment of poorly-controlled type 2 diabetes mellitus. Intensified insulin treatment gradually normalizeed blood glucose, but on the 19th hospital day, after a blood glucose measurement of 49 mg/dL, she showed hemichorea of the left face, shoulder, arm and leg. MRI revealed no abnormalities of either the putamen or the striatum on T1-weighted images. She was treated with dopamine receptor antagonists, which alleviated her hemichorea symptoms and allowed discharge from the hospital. 1 year after the first hospitalization, she had to be readmitted because her glycemic control had markedly deteriorated. Glycemic control improved rapidly, and, because hemichorea did not recur, the dopamine receptor antagonists were stopped. 1 month later, however, hemichorea recurred. She resumed taking the dopamine receptor antagonists, resulting in immediate disappearance of the hemichorea. CONCLUSIONS: We herein describe a rare case of diabetes-associated hemichorea occurring after hypoglycemic episodes without abnormal high-intensity findings in the basal ganglia on T1-weighted images. The hemichorea relapsed with cessation of dopamine receptor antagonists. This case also underscores the importance of longitudinal assessment and treatment for hemichorea after hypoglycemic episodes, even in the absence of MRI findings, in elderly diabetic patients.

Relation between Resting State Front-Parietal EEG Coherence and Executive Function in Parkinson's Disease.

Objective. To assess the relation between executive dysfunction (ED) in Parkinson's disease (PD) and resting state functional connectivity evaluated using electroencephalography (EEG) coherence. Methods. Sixty-eight nondemented sporadic PD patients were assessed using the Behavioural Assessment of the Dysexecutive Syndrome (BADS) to evaluate executive function. EEG coherence in the left frontoparietal electrode pair (F3-P3) and the right frontoparietal electrode pair (F4-P4) was analyzed in the alpha and theta range. The BADS scores were compared across the coherence groups, and the multiple logistic regression analysis was performed to assess the contribution of confounders. Results. The standardized BADS score was significantly lower in the low F3-P3 coherence group in the alpha range (Mann-Whitney U test, p = 0.032), though there was no difference between F4-P4 coherence group in the alpha range, F3-P3, and F4-P4 coherence groups in the theta range and the standardized BADS score. The multiple logistic regression analysis revealed the significant relation between the F3-P3 coherence group in alpha range and age-controlled standardized BADS score (p = 0.039, 95% CI = 1.002-1.062). Conclusion. The decrease in resting state functional connectivity between the frontal and parietal cortices especially in the left side is related to ED in PD.

Corynebacterium lowii sp. nov. and Corynebacterium oculi sp. nov., derived from human clinical disease and an emended description of Corynebacterium mastitidis.

Strains of members of the genus Corynebacterium derived from ophthalmologic patients in Japan, Belgium and Switzerland and found to be closely related to-, but distinguishable from Corynebacterium mastitidis by 16S rRNA gene sequencing, were characterized using biochemical, chemotaxonomic, MALDI-TOF mass spectrometry and antimicrobial susceptibility methods and DNA-DNA hybridization as well as by whole-genome sequencing (WGS). Based on this investigation, we describe Corynebacterium lowii sp. nov. and Corynebacterium oculi sp. nov., derived from human ocular specimens, as well as emend the description of Corynebacterium mastitidis. Type strains for these species are: C. lowii R-50085T (=LMG 28276T =CCUG 65815T) and C. oculi R-50187T (=LMG 28277T =CCUG 65816T). DNA G+C content was found to be 62.2 % (by HPLC) and 62.8 % (by WGS) for C. lowii R-50085T, 64.1 % (HPLC) and 64.8 % (WGS) for C. oculi R-50187T and 67.8 % (HPLC) for C. mastitidis LMG 19040T [=S-8T =CCUG 38654T =CECT 4843T =CIP 105509T =DSM 44356T =IFO (NBRC)16160T =JCM 12269T].

Relationship between Postural Deformities and Frontal Function in Parkinson's Disease.

Postural deformities and executive dysfunction (ED) are common symptoms of Parkinson's disease (PD); however, the relationship between postural deformities and ED in patients with PD remains unclear. This study assessed the relationship between postural deformities and ED in patients with PD. Sixty-five patients with sporadic PD were assessed for the severity of postural deformities and executive function. The severity of postural deformities was scored using the United Parkinson's Disease Rating Scale item 28 score: no postural deformity (0), mild postural deformities (1), or severe postural deformities (2-4). Executive function was assessed using the Behavioral Assessment of the Dysexecutive Syndrome (BADS) and an age-controlled standardized BADS score <70 was defined as ED. Age-controlled standardized BADS scores were compared across the three groups using the Kruskal-Wallis test. Relationship between ED and the severity of postural deformities was assessed using the Mann-Whitney U test. Age-controlled standardized BADS score significantly differed among the three groups (P = 0.005). ED was significantly related to the severity of postural deformities (P = 0.0005). The severity of postural deformities was associated with a lower age-controlled standardized BADS score and ED, and these findings suggest that postural deformities were associated with frontal dysfunction in patients with PD.

Relation between freezing of gait and frontal function in Parkinson's disease.

INTRODUCTION: Freezing of gait (FOG) is a common symptom of Parkinson's disease (PD). Although the pathophysiological mechanism of FOG is unknown, previous studies have suggested that frontal dysfunction is associated with FOG. The Behavioral Assessment of the Dysexecutive Syndrome (BADS) battery, which is wide-ranging neurological battery composed of six subtests, evaluates frontal function and is more sensitive to executive dysfunction (ED) than other tools in PD patients. This is the first study to assess the relation between FOG in the 'on' state and frontal dysfunction evaluated using BADS. METHODS: Subjects were 65 patients with PD. Multiple logistic regression analysis was used to compare the age-controlled standardized BADS score, age, disease duration, Hoehn and Yahr (HY) stage, levodopa-equivalent daily dose, and Mini-Mental State Examination (MMSE) score across patients with FOG (n = 43) and patients without FOG (n = 22). Score on each of the six BADS subtests were compared across patients with and without FOG using the Mann-Whitney U test. RESULTS: Multiple logistic regression analysis revealed that FOG was related to lower age-controlled standardized BADS score (P = 0.022) and higher HY stage (P = 0.009) but not to disease duration, levodopa equivalent daily dose, or MMSE score. Among the six BADS subtests, score on the Zoo Map Test, which evaluates problem solving and planning, was lower in patients with FOG than in patients without FOG. CONCLUSION: These results support a relation between on-state FOG and frontal dysfunction in PD patients.

Multicentre clinical study of the herpes simplex virus immunochromatographic assay kit for the diagnosis of herpetic epithelial keratitis.

BACKGROUND/AIMS: The novel immunochromatographic assay (ICGA) kit was recently developed to diagnose herpes simplex virus (HSV) infection. This multicentre study aimed to evaluate the value of the ICGA kit for the diagnosis of herpetic epithelial keratitis by comparing it with immunofluorescence assay (IFA) and real-time PCR. METHODS: Corneal scrapings were collected from 117 patients, including 77 with herpetic keratitis as their final clinical diagnosis as well as 40 others at 21 facilities. These samples were tested by the ICGA kit, IFA and real-time PCR. RESULTS: The positive concordance between final clinical diagnosis and ICGA was 46.7% (35/75 cases) and the negative concordance was 100% (39/39). The positive and negative concordance between real-time PCR and ICGA were 57.4% (35/61 cases) and 100% (53/53), respectively. The positive and negative concordance between IFA and ICGA were 61.1% (22/36 cases) and 83.3% (55/66), respectively. In 92 cases where anti-HSV drugs were not prescribed prior to corneal scraping, the positive and negative concordance between final clinical diagnosis and ICGA were 55.0% (33/60 cases) and 100% (32/32), respectively. CONCLUSIONS: The ICGA kit has moderate sensitivity and high specificity, indicating clinical utility in the diagnosis of herpetic epithelial keratitis.

Current perception threshold in subacute myelo-optico-neuropathy.

We report the first current perception threshold (CPT) examination of sensory disturbance in subacute myelo-optico-neuropathy (SMON). SMON patients experience serious neurological symptoms, including dysesthesia, sensory loss, motor weakness, and visual impairment. During CPT examination, 5 Hz, 250 Hz, and 2,000 Hz stimulations were used to stimulate C fibers, A-delta fibers, and A-beta fibers, respectively. Ten SMON patients (mean age, 73.8 +/- 8.4 years) and ten age-matched controls (72.3 +/- 6.3 years) were studied using CPT measured at the index finger and near the external malleolus. The CPTs to 250 Hz and 2,000 Hz stimulations near the external malleolus were significantly higher and the CPT to 5 Hz stimulation was significantly lower in the SMON group than in the control group. Although peripheral nerve impairment is mild in SMON, pathological examination shows a decrease of large fibers. This is thought to increase the CPTs to 250 Hz and 2,000 Hz stimulations. The center of the gate control of pain exists in the posterior horn receiving information from the dorsal root ganglion. The dorsal root ganglion at the lumber cord is strongly impaired in SMON; therefore, the gate control may not work effectively, and decreases CPT to 5 Hz stimulation.

The inhibitory effect of vancomycin ointment on the manifestation of MRSA keratitis in rabbits.

The purpose of this study was to investigate an experimental model of methicillin-resistant Staphylococcus aureus (MRSA) keratitis, and to evaluate the inhibitory effect of vancomycin ointment on the manifestation of keratitis in this model. For the development of the MRSA keratitis model, 16 rabbits received 0.3-ml intrastromal injections of 1 x 10(7) colony forming units/ml MRSA inoculated to each of their corneas. After the MRSA inoculation, the rabbits were examined for a period of 14 days. Vehicle only was applied to each left eye for 2 days as an experimental control. Prototype vancomycin ointments, at concentrations of 0.03%, 0.1%, 0.3%, and 1.0%, were applied to each right eye for 2 days. The treatment commenced immediately after the MRSA inoculation and was administered five times a day at 2-h intervals. Four rabbits were used for each vancomycin ointment concentration. Anterior segments were examined daily, and the minimum inhibitory concentration of vancomycin (percentage in the ointment) for treating MRSA keratitis was determined on day 2. On day 14, no recurrences of infection were observed in the eyes that had not exhibited keratitis on day 2. Forty-eight hours post-inoculation, all left eyes demonstrated severe conjunctivitis, stromal infiltrates at injection sites, and fibroid reactions in the anterior chamber. MRSA keratitis was completely inhibited by 0.3% and 1.0% vancomycin ointments. Although the 0.1% ointment generally could prevent keratitis, punctate infiltrates were found in some eyes. Numerous infiltrates were found in eyes treated with 0.03% ointment. In conclusion, the present study substantiates the view that vancomycin ointment has a potent inhibitory effect upon the manifestations of MRSA keratitis, and indicates that a 0.3% concentration is necessary for effective treatment.

Low susceptibility to N-ethyl-N-nitrosourea-induced transplacental carcinogenesis in Long-Evans Cinnamon (LEC) rats.

The Long-Evans Cinnamon (LEC) rat, an animal model of Wilson's disease, is resistant to a variety of chemical carcinogenesis except liver and colon. In the present study, N-ethyl-N-nitrosourea (ENU)-induced transplacental carcinogenesis was examined in male and female LEC, Long-Evans Agouti (LEA), a sibling line of the LEC rat, and F344 rats (n=21). ENU was administered to pregnant rats as a single s.c. injection at a dose of 60 mg/kg body weight on the 17th day after conception. Cerebral/spinal gliomas and trigeminal/spinal nerve schwannomas developed in both LEA and F344 rats at 30 weeks of age, but no nervous system tumors developed in LEC rats, the difference being statistically significant. Lung adenomas also developed in LEA and F344 rats, but not in LEC rats. Semiquantitative RT-PCR demonstrated that metallothionein (MT)1a, MT2 and O(6)-methylguanine-DNA methyltransferase (MGMT) mRNA levels in the liver of LEC rats were higher than those in F344 and LEA rats. In addition, Western blot analysis showed that MT (MT1 plus MT2) in the liver of LEC rats was also higher than that in other strains. Present results suggest that high levels of MT and/or MGMT contribute to the resistance to nitrosamine-induced carcinogenesis in LEC rats.

Efficacy of combined photodynamic therapy and sub-Tenon's capsule injection of triamcinolone acetonide for age-related macular degeneration.

PURPOSE: To evaluate the efficacy of combined photodynamic therapy (PDT) and sub-Tenon's capsule injection of triamcinolone acetonide (TA) for the treatment of choroidal neovascularization (CNV) in age-related macular degeneration (AMD) at 1-year follow-up. METHODS: A total of 117 eyes with subfoveal CNV caused by AMD were included. Sixty-eight eyes were treated with combined PDT and sub-tenon injection of 20 mg TA and compared with a control group of 49 eyes treated with PDT alone. All patients completed 1 year follow-up. The main outcome measures were best-corrected visual acuity (BCVA) and retreatment frequency. RESULTS: There were no significant differences in age, sex, VA, lesion type, and greatest linear dimension between the two groups at baseline. BCVA analysis showed statistically no significant differences between the two groups. The PDT+TA group required a lower mean number of treatments (1.38 versus 1.67, P=0.032). CONCLUSION: Our study confirms that sub-Tenon's capsule injection of TA with PDT significantly reduces the retreatment frequency of PDT.

Efficacy of intravitreal bevacizumab (Avastin) for short-term treatment of diabetic macular edema.

PURPOSE: To report the efficacy of intravitreal injections of bevacizumab for diabetic macular edema (DME) in the short-term. DESIGN: Retrospective, noncomparative, interventional case series. METHODS: Medical records of 20 eyes of 19 patients who underwent intravitreal injections of bevacizumab for persistent diabetic macular edema were reviewed retrospectively. All eyes received intravitreal injections of bevacizumab (1.25 mg/0.05 ml). The clinical course of best-corrected visual acuity (BCVA) using a logarithm of the minimum angle of resolution chart, and averaged foveal retinal thickness using an optical coherence tomography (OCT) were monitored for up to four weeks after the injection. RESULTS: BCVA at one week improved by two lines or more in six eyes (30%) and in nine eyes (45%) at four weeks. However, no significant improvement in the mean BCVA from baseline was observed at one week (P>0.05) and four weeks (P>0.05). Mean retinal thicknesses (RT) were 411+/-170 mum at baseline, 349+/-102 microm at one week after the injection (P<0.05), and 380+/-159 microm at four weeks (P>0.05). One week after the injection, significant regression of macular edema was seen. However, recurrence occurred at four weeks. No complications such as severe vision loss, endophthalmitis, or systemic events developed. CONCLUSION: No changes in BCVA and RT were observed in the short-term observation after the intravitreal injection of bevacizumab for DME.

Three cases of Acanthamoeba keratitis diagnosed and treated in the early stage.

Acanthamoeba keratitis (AK) is a severe infectious corneal ulcer that usually occurs in contact lens wearers. Although the number of AK cases in Japan has been increasing, many of these cases are diagnosed in the early stage and are treated adequately. This is probably because of the increased availability of various diagnostic techniques and the ever-increasing knowledge about AK among ophthalmologists. In this article, we described 3 cases of AK that were diagnosed and treated in the early stages of the disease, and we discuss why 1 of the cases had a less favorable prognosis than the other 2 cases, which had excellent prognoses, from an etiological point of view.

Influenza vaccine with Surfacten, a modified pulmonary surfactant, induces systemic and mucosal immune responses without side effects in minipigs.

Immune responses and side effects of intranasally administered flu vaccine with the commercial product Surfacten, a modified bovine pulmonary surfactant, were investigated in minipigs. The use of minipigs was based on the anatomical resemblance of nasal lymph nodes, the principal antigen uptake site of respiratory mucosal immunity, between pig and human. Intranasal instillation of HA vaccine adjuvanted with Surfacten elicited significantly higher serum hemagglutination inhibition titers than the antigen alone, with wide cross-neutralizing activities of secretory IgA in nasal washes. No significant induction of inflammatory cytokines or migration of inflammatory cells was observed at the site of immunization or serum after the first immunization. These data suggest the potential usefulness of Surfacten for mucosal vaccination.

A novel ultra-sensitive enzyme immunoassay for soluble human insulin receptor ectodomain and its measurement in urine from healthy subjects and patients with diabetes mellitus.

OBJECTIVE: For the early identification of patients at risk of developing diabetes mellitus, and to prevent the onset of diabetes by performing dietary counseling and exercise guidance, we have developed an ultra-sensitive immune complex transfer enzyme immunoassay (ICT-EIA) to measure soluble human insulin receptor ectodomain (sIRalpha) in urine which is collected non-invasively. DESIGN AND METHODS: We developed ICT-EIA for sIRalpha and measured urinary sIRalpha from 106 healthy volunteers, 35 obese volunteers and 42 patients with diabetes. RESULTS: The detection limit of ICT-EIA (0.04 pg/mL), using a urine sample of as little as 100 microL, was a few hundred-fold higher than that of conventional ELISA. Using ICT-EIA, the urinary sIRalpha level in patients with diabetes (9.7+/-20.1 pg/mg creatinine) was significantly higher than those in healthy volunteers (1.4+/-0.9; P<0.001). CONCLUSION: ICT-EIA for sIRalpha may be useful as a good marker for evaluating diabetes risk.

Association of HTRA1 mutations and familial ischemic cerebral small-vessel disease.

BACKGROUND: The genetic cause of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), which is characterized by ischemic, nonhypertensive, cerebral small-vessel disease with associated alopecia and spondylosis, is unclear. METHODS: In five families with CARASIL, we carried out linkage analysis, fine mapping of the region implicated in the disease, and sequence analysis of a candidate gene. We also conducted functional analysis of wild-type and mutant gene products and measured the signaling by members of the transforming growth factor beta (TGF-beta) family and gene and protein expression in the small arteries in the cerebrum of two patients with CARASIL. RESULTS: We found linkage of the disease to the 2.4-Mb region on chromosome 10q, which contains the HtrA serine protease 1 (HTRA1) gene. HTRA1 is a serine protease that represses signaling by TGF-beta family members. Sequence analysis revealed two nonsense mutations and two missense mutations in HTRA1. The missense mutations and one of the nonsense mutations resulted in protein products that had comparatively low levels of protease activity and did not repress signaling by the TGF-beta family. The other nonsense mutation resulted in the loss of HTRA1 protein by nonsense-mediated decay of messenger RNA. Immunohistochemical analysis of the cerebral small arteries in affected persons showed increased expression of the extra domain-A region of fibronectin and versican in the thickened tunica intima and of TGF-beta1 in the tunica media. CONCLUSIONS: CARASIL is associated with mutations in the HTRA1 gene. Our findings indicate a link between repressed inhibition of signaling by the TGF-beta family and ischemic cerebral small-vessel disease, alopecia, and spondylosis.

Prognostic value of cerebrospinal fluid cytokine changes in herpes simplex virus encephalitis.

A recent trial suggested that corticosteroid was beneficial in herpes simplex virus encephalitis (HSVE), but that precise role remains unclear. We assessed the differences of cerebrospinal fluid (CSF) cytokine changes between different outcomes and between patients with and without corticosteroid administration at the acute stage of HSVE. Interleukin (IL)-1beta, IL-2, IL-6, IL-10, interferon (IFN)-gamma, and tumor necrosis factor-alpha were measured in 56 serial CSFs taken from 20 adult HSVE patients. Their outcomes were poor in 7 and good in 13 patients, and corticosteroid was administered in 10. The differences in the initial and maximum cytokine values were assessed among the different outcomes. The decline rate of cytokine values between the initial and second CSF samples was also assessed between patients with and without corticosteroid. The initial IFN-gamma and maximum IL-6 with a poor outcome were higher than those with a good outcome (p=0.019 for IFN-gamma and p=0.013 for IL-6). The decline rate of IL-6 in patients with corticosteroid was higher than that without corticosteroid (p=0.034). The initial IFN-gamma and maximum IL-6 CSF values represented prognostic biomarkers in HSVE. One pharmacological mechanism related to corticosteroid in HSVE is apparently inhibition of pro-inflammatory cytokines such as IL-6.

Are topical steroids essential after an uneventful cataract surgery?

PURPOSE: To access the necessity of topical steroids after uneventful cataract surgery, phaco-emulsification/aspiration plus intraocular lens (PEA+IOL) implantation. DESIGN: Single-blind, randomized, prospective study. PARTICIPANTS: Twenty-one patients were prospectively randomized, 11 patients were assigned to the steroid group, and 10 to the non-steroid group. METHODS: Between March and September 2007, in Mino Tanaka Hospital in Tokushima Prefecture, Japan, we performed PEA+IOL in 28 eyes of 21 patients and examined the visual acuity, corneal endothelium cell density, and anterior aqueous flare value after dividing all the patients into 2 groups, the topical steroid use and the non-steroid group. RESULTS: At 1 month postoperatively, no difference was observed between the 2 groups in terms of the outcomes described, and no cystoid macular edema was detected. CONCLUSION: Topical steroid medication may not be absolutely essential after uneventful PEA+IOL.

Hospital-based study of the prognostic factors in adult patients with acute community-acquired bacterial meningitis in Tokyo, Japan.

BACKGROUND: Prognostic factors related to community-acquired bacterial meningitis (BM) in adult patients have been evaluated using multivariate analysis in The Netherlands, where the rate of antibiotic resistance was low. However, an evaluation of these factors in countries with a high rate of antibiotic resistance has not yet been done. Thus, we studied the prognostic factors in adults with community-acquired BM in our hospitals, which are located in Tokyo, Japan, where the rate of antibiotic resistance is high. METHODS: We selected 71 consecutive adult patients with community-acquired BM in which the pathogens were identified and then classified the patients into two groups based on the Glasgow Outcome Scale: a favorable outcome group (n=48), and an unfavorable outcome group (n=23). Their clinical and laboratory variables were analyzed using single logistic regression analysis followed by multiple logistic regression analysis. RESULTS: The overall mortality rate was 23%. The rate of antibiotic resistance was 54.9%. The most common resistant bacteria were penicillin-resistant Streptococcus pneumoniae, followed by methicillin-resistant Staphylococcus aureus. The Glasgow Coma Scale score (GCS) at the initiation of antibiotic therapy and a low thrombocyte count were identified as significant unfavorable prognostic factors (GCS: p=0.020, odds ratio=0.528, 95%CI=0.309-0.902; thrombocyte count: p=0.037, odds ratio=0.802, 95%CI=0.652-0.987). The presence of antibiotic-resistant bacteria was not identified as a prognostic factor. CONCLUSION: Patients with a low GCS at the initiation of antibiotic therapy and low thrombocyte counts had unfavorable outcomes. With appropriate antibiotic administration, the antibiotic-resistant bacteria were not identified as an unfavorable prognostic factor, even in an area with a high rate of antibiotic resistance.

Jagged1 suppresses collagen-induced arthritis by indirectly providing a negative signal in CD8+ T cells.

Distinct Notch ligands possess a characteristic ability in terms of functional T cell differentiation. However, the precise role or the therapeutic potential of each Notch ligand in autoimmune diseases is largely unknown. In this study, we examined whether Jagged1 modulates a collagen-induced rheumatoid arthritis (CIA) model by altering T cell responses. The injection of a soluble Jagged1-encoding plasmid, sJag1-P, before or even after initial type II collagen (CII) immunization suppressed the disease severity of CIA. However, this treatment did not suppress CII-specific CD4(+) T cell proliferation and CII-specific Ab production. Depletion of either CD4(+) or CD8(+) T cells ameliorated CIA severity and sJag1-P further improved CIA in CD4(+) but not CD8(+) T cell-depleted mice. Injection of OVA and Jagged1-encoding plasmids inhibited proliferation of OVA-specific granzyme B-producing CD8(+) T cells, although Jagged1 could not directly inhibit CD8(+) T cell proliferation in vitro. The blockade of Jagged1 by an anti-Jagged1 Ab exacerbated CIA, whereas this effect was not observed in the absence of CD8(+) T cells. These data indicate that Jagged1 is able to deliver an indirect negative signal into CD8(+) T cells in vivo, which suggests its therapeutic potential in the treatment of CD8(+) T cell-mediated diseases, including rheumatoid arthritis.