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Biomedical subjects

Nobuyoshi Kitaichi

Publications and source records attributed to Nobuyoshi Kitaichi.

18 recordsLinked to original sources
PubMed2007

The positive role of lumbar puncture in the diagnosis of Vogt-Koyanagi-Harada disease: lymphocyte subsets in the aqueous humor and cerebrospinal fluid.

PURPOSE AND METHODS: Activated T cells are believed to be important at the inflammatory sites in the pathogenesis of Vogt-Koyanagi-Harada disease. Patients are often affected by meningitis and uveitis. In this work, to examine the positive role of lumbar puncture in the diagnosis of VKH disease, we analyzed and compared the surface markers of aqueous humor cells, cerebrospinal fluid cells, and peripheral blood lymphocytes by use of flow cytometry. RESULTS: Most lymphocytes were T cells. In aqueous humor and cerebrospinal fluid, numbers of CD3(+), CD4(+), and CD4(+)CD45RO(+) cells were significantly greater than in peripheral blood lymphocytes (P < 0.01). The CD4(+)/CD8(+) ratio for aqueous humor and cerebrospinal fluid was significantly higher than that for peripheral blood cells (P < 0.01). Four weeks after starting systemic corticosteroid treatment, numbers of CD4(+) and CD4(+)CD45RO(+) cells in cerebrospinal fluid were significantly lower than before treatment. CONCLUSIONS: Profiles of surface markers were similar for cerebrospinal fluid and aqueous humor, but apparently different from that for peripheral blood cells. This suggests that cerebrospinal fluid may reflect the active local immunological reaction at sites affected by the disease, i.e. the uvea and the meninges.

Acute Disease↗
PubMed2006

Amelioration of experimental autoimmune uveoretinitis (EAU) with an inhibitor of nuclear factor-kappaB (NF-kappaB), pyrrolidine dithiocarbamate.

Experimental autoimmune uveoretinitis (EAU) is a T helper type 1 cell-mediated autoimmune disease, which serves as a model of human chronic uveitis. In this model, cells of a monocyte/macrophage lineage and retinal antigen (Ag)-specific T cells infiltrate into the retina and cause inflammatory lesion, where proinflammatory cytokines and various stimuli activate a transcriptional factor, nuclear factor-kappaB (NF-kappaB), which modulates inflammation and enhances immune responses. In the present study, the therapeutic effect of administration of a NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC), was examined in a murine EAU model. It was shown that PDTC ameliorated the clinical symptoms of EAU mice and significantly reduced the histopathological score compared with those in untreated mice. mRNA expressions of tumor necrosis factor alpha and interleukin-1beta were suppressed in eyes of PDTC-treated EAU mice. However, when T cells from PDTC-treated EAU mice, Ag-presenting cells (APC), and the retinal Ag peptides were cocultured, these T cells showed the same level of proliferation as those from control mice. Furthermore, addition of PDTC in the culture of T cells from EAU mice, Ag, and APC completely abrogated the T cell-proliferative response and cytokine production. Pretreatment of Ag-primed T cells or APC with PDTC in vitro also reduced these responses. These results indicate that the inhibitory effect of PDTC is attributed mainly to the suppression of effector-phase responses including inflammation but not to the inhibition of T cell priming. Regulation of NF-kappaB pathway in the lesion could be a novel target for the successful control of uveoretinitis.

Amino Acid Sequence↗
PubMed2006

Elevation of serum Krebs von den Lunge-6 levels in patients with tubulointerstitial nephritis and uveitis syndrome.

BACKGROUND: Tubulointerstitial nephritis and uveitis (TINU) syndrome is characterized by a combination of idiopathic acute tubulointerstitial nephritis and uveitis. Krebs von den Lunge-6 (KL-6) is a human glycoprotein secreted by type II alveolar cells in the lung, and its serum levels increase in patients with pneumonia of various causes, as well as ocular sarcoidosis. The aim of the present study is to quantify serum KL-6 levels in patients with TINU syndrome, which has no pulmonary and sarcoid lesions, and elucidate the usefulness of KL-6 for the diagnosis and follow-up of this syndrome. METHODS: Serum and urinary samples were obtained from 17 patients with TINU syndrome and 36 age-matched patients with uveitis from other causes. Sarcoidosis was eliminated because serum KL-6 levels increased during their lung lesion. Serum KL-6 level was determined by using a human KL-6 electrochemiluminescence immunoassay. Formalin-fixed paraffin-embedded renal tissue sections were incubated with anti-KL-6 monoclonal antibody, then examined immunohistochemically. RESULTS: Mean serum KL-6 levels for patients with TINU syndrome and those with uveitis from other causes were 363.35 +/- 51.06 and 213.19 +/- 10.28 U/mL, respectively (P < 0.001). Urinary beta(2)-microglobulin levels of patients with TINU syndrome and uveitis from other causes were 4.06 +/- 1.31 and 0.16 +/- 0.20 mg/L, respectively (P < 0.001). All patients with TINU syndrome showed a simultaneous decrease in serum KL-6 and urinary beta(2)-microglobulin levels after the beginning of treatment. Strong immunoreactivity for KL-6 was observed in renal distal tubules in biopsy tissue of patients with TINU syndrome. CONCLUSION: We show a significant increase in serum KL-6 levels in patients with TINU syndrome, whereas levels were normal in patients with other causes of uveitis without nephritis. Renal distal tubules stained strongly with anti-KL-6 antibody, suggesting that high KL-6 levels may reflect the renal lesion of TINU syndrome. Serum KL-6 may be a potential laboratory parameter for the diagnosis and follow-up of patients with TINU syndrome that could complement urinary beta(2)-microglobulin measurements.

Adolescent↗
PubMed2006

Phosphorylation of p27(KIP1) in lens epithelial cells after extraction of fiber cells.

Opacification of the posterior capsule depends on replication of the residual lens epithelial cells lining the capsule. However, the mechanisms in the regulation of lens cell proliferation have not been determined. The purpose of this study is to examine the expression of p27(KIP1), a cyclin-dependent kinase inhibitor, and its phosphorylation, and cyclin D1 in lens epithelial cells after extraction of fiber cells. C57Bl6 mice (12 weeks old) were anesthetized, and the lens fiber cells were surgically extracted. Eyeballs were collected and fixed at 15 min and 24 h after extraction with and without injection of a specific phosphorylated extracellular signal-regulated kinase (pERK) 1/2 inhibitor (PD98059) to the anterior chamber. Collected tissues were analyzed using immunohistochemistry with anti-p27(KIP1), anti-phosphorylated p27(KIP1) on serine 10 (s10-phospho-p27) and cyclin D1 antibodies. Human lens epithelial cells were cultured, and then were treated with and without 40 ng/ml human recombinant basic fibroblast growth factor (bFGF), which was analyzed by Western blot analysis. In the untreated lens, p27(KIP1) was not phosphorylated in the lens epithelial cells, although p27(KIP1)-positive nuclei were detected in the lens cells of the equatorial region. Immunoreactivity for cyclin D1 was hardly detected in the lens. Nuclear immunoreactivity for p27(KIP1) and s10-phospho-p27 was observed in several lens cells of the equatorial region 15 min after extraction of fiber cells. Western blotting demonstrated that the p27(KIP1) phosphorylation form was upregulated 15 min after bFGF treatment in cultured lens epithelial cells. Many cyclin D1-positive nuclei were noted 24 h after the surgery. p27(KIP1) phosphorylation and cyclin D1 induction were inhibited by PD98059. s10-phospho-p27 and p27(KIP1) immunoreactivity was undetected in the lens cells 24 h after the extraction of fiber cells. It is possible that the phosphorylation of p27(KIP1), and cyclin D1 expression are regulated by the ERK pathway in lens cells after the extraction of fiber cells.

Animals↗
PubMed2005

Increase in macrophage migration inhibitory factor levels in lacrimal fluid of patients with severe atopic dermatitis.

BACKGROUND AND AIMS OF THE STUDY: Atopic dermatitis is a chronic inflammatory skin disorder that often involves some ophthalmic features. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that is associated with the generation of cell-mediated immune responses. Although serum MIF levels may be elevated in severe atopic dermatitis, the quantity of MIF in regional ocular fluid remains unknown. We measured MIF levels in tears (lacrimal fluid) of patients with atopic dermatitis. PATIENTS AND METHODS: Tear samples were collected from 16 patients with atopic dermatitis, 10 patients with allergic conjunctivitis, and 15 healthy control subjects. The clinical severity of atopic dermatitis was evaluated according to the Scoring Atopic Dermatitis (SCORAD) index. The index was calculated by summing the following scores: extent criteria, intensity criteria, and subjective symptoms. Macrophage migration inhibitory factor levels were determined by a human MIF enzyme-linked immunosorbent assay. All comparisons were two-tailed, and P values <0.01 were considered as statistically significant. RESULTS: The mean MIF concentration in lacrimal fluid collected from healthy control subjects was 0.69+/-0.2 ng/ml. The mean tear MIF levels were 17.87+/-6.3 ng/ml in moderate-to-severe atopic dermatitis (SCORAD> or =15, P=0.002), 0.93+/-0.08 ng/ml in mild atopic dermatitis (SCORAD<15), and 2.76+/-0.86 ng/ml in allergic conjunctivitis (P=0.008). CONCLUSIONS: A proinflammatory cytokine MIF level was elevated in tears as well as serum in cases of severe atopic dermatitis. These results suggest that MIF may play an important role in the induction or enhancement of ophthalmic features related to severe atopic dermatitis.

Adolescent↗
PubMed2005

Immunolocalization of cyclin D1 in the developing lens of c-maf -/- mice.

The maf gene encodes a transcription factor protein containing a typical basic/leucine zipper domain structure, a motif for protein dimerization and DNA binding. It has been demonstrated that maf family genes have important roles in embryonic development and cellular differentiation. In this study, localization of cyclin D1, one of the cell cycle-related molecules, was examined immunohistochemically in developing lens cells of c-maf knockout (-/-) mice. At embryonic day 14 in wild-type mice, lens cells consisted of round epithelial cells in a single layer and regularly arranged elongated lens cells, indicating primary lens fiber cells. Cyclin D1-positive nuclei were observed in the lens epithelial cells, whereas cyclin D1 was not detected in the primary lens fiber cells. In c-maf -/- mice, a variety of round epithelial cells were located in the anterior and posterior lens. Many cyclin D1-positive nuclei were observed in lens epithelial cells as well as posterior lens cells. These results are consistent with c-maf playing a role in the regulation of cyclin D1 in developing lens cells.

Animals↗
PubMed2005

Usefulness of quantifying serum KL-6 levels in the follow-up of uveitic patients with sarcoidosis.

BACKGROUND: KL-6 is a human glycoprotein secreted by type II alveolar cells in the lung, and its serum levels increase in pneumonia of various causes. We previously reported that serum KL-6 levels in uveitis patients with sarcoidosis were significantly higher than those of other uveitis patients and healthy controls. Additionally, the combined measurement of serum KL-6 and angiotensin converting enzyme (ACE) was useful for screening uveitic patients to diagnose sarcoidosis. The purpose of the present study was to investigate the clinical usefulness of quantifying serum KL-6 levels for following-up the patients with sarcoidosis. METHODS: Sera were obtained from 36 uveitic patients diagnosed with sarcoidosis and the same number of healthy volunteers. To examine the influence of systemic medication, we also collected blood samples from four more sarcoidosis patients, who were systemically treated with corticosteroid or angiotensin converting enzyme (ACE) inhibitor, an anti-hypertensive drug. The serum concentration of KL-6 was measured by a human KL-6 electrochemiluminescence immunoassay (ECLIA). RESULTS: The mean KL-6 concentrations of sarcoidosis patients and healthy controls were 449.3+/-66.3 (mean+/-SE) and 192.1+/-11.3, respectively. The average levels of serum KL-6 were significantly elevated in sarcoidosis patients compared with healthy control subjects (P<0.001), and there were significant correlations between serum KL-6 and ACE levels in the patients with sarcoidosis (r=0.70 and P<0.0001). Moreover, serum KL-6 concentrations were less affected by systemic corticosteroid, and unaffected by ACE inhibitory drugs in contrast to ACE levels. CONCLUSIONS: Measurement of serum KL-6 in the uveitic patients may be useful to follow-up the diagnosed sarcoidosis, as well as for diagnosing sarcoidosis, because the serum KL-6 level was well correlated with the ACE level, and less affected by systemic medication than ACE levels.

Adult↗
PubMed2005

Inducible immune regulation following autoimmune disease in the immune-privileged eye.

The immune-privileged eye has the potential to induce regulatory immunity along with local mechanisms of immunosuppression. Rodent models of human autoimmune uveoretinitis [experimental autoimmune uveoretinitis (EAU)] recover without spontaneous recurrence of uveitis, which differs from uveitis in some humans. This raises the possibility that the mechanism of immune privilege in the rodent eye can reimpose itself during autoimmune uveoretinitis and re-establish tolerance to autoantigen. To investigate this possibility, we examined the spleens of EAU-recovered mice for regulatory immunity. We detected regulatory immunity when we adoptively transferred post-EAU spleen cells into other mice immunized for EAU. We could not detect this regulatory immunity in enucleated mice nor in naive mice. Moreover, unlike the mechanisms of anterior chamber-associated immune deviation, the suppression was only mediated by post-EAU CD4+ T cells, which required activation with autoantigen presented by post-EAU spleen antigen-presenting cells (APC). Our results demonstrate that when the immune-privileged ocular microenvironment recovers from an autoimmune response, it has influenced systemic immunity to retinal autoantigen by affecting APC and mediating induction of potential regulatory CD4+ T cells laying in wait in the post-EAU spleen for restimulation.

Animals↗
PubMed2005

Comparative study of two sets of criteria for the diagnosis of Vogt-Koyanagi-Harada's disease.

PURPOSE: The Vogt-Koyanagi-Harada's (VKH) Disease Committee established the "Revised diagnostic criteria for VKH disease" in 2001. The purpose of the present study was to assess the concordance between these criteria and the traditional Sugiura's diagnosis system. DESIGN: Observational case series. METHODS: The medical records of patients previously diagnosed with VKH disease based upon Sugiura's criteria at the Uveitis Survey Clinic of the Hokkaido University Hospital between 1991 and 2003 were retrospectively reevaluated using the VKH Committee's revised diagnostic criteria for VKH disease. RESULTS: Sugiura's criteria were used to identify 169 patients with VKH disease. All patients were Japanese, and 95 cases (56%) were women. Mean age at the time of their first visit to our clinic was 44.7 +/- 13.9 years (range, 9 to 74 years). Using the VKH Committee's new criteria, 91.7% of the previously diagnosed VKH patients were classified as having the disease. Of this group, 11.8% were classified as complete, 71% incomplete, and 8.9% as probable VKH disease. CONCLUSIONS: The VKH Committee's revised diagnostic criteria proved useful for VKH disease diagnosis, as the concordance rate for the two criteria was more than 90%. However, patients who had prior cataract surgery or who lacked signs of serous retinal detachment were not classified as having VKH disease because of exclusion by the VKH Committee's new criteria.

Adolescent↗
PubMed2005

Clinical features in tubulointerstitial nephritis and uveitis (TINU) syndrome.

PURPOSE: To analyze clinical features of the tubulointerstitial nephritis and uveitis (TINU) syndrome in Japan, especially exacerbations or recurrences of uveitis. DESIGN: Retrospective observational study. METHODS: We reviewed the clinical features in 12 patients with TINU syndrome diagnosed by renal biopsy, who were evaluated and treated at the Department of Ophthalmology, Hokkaido University Hospital. Visual acuity was measured using decimal visual acuity. RESULTS: Patient age ranged from 10 to 33 years (mean 21 years), and females accounted for 83% of the cases. Both eyes were affected in 11 patients (92%). All 12 patients initially experienced ocular symptoms, with hyperemia being the chief complaint. We diagnosed patients as having uveitis and conducted blood tests and urinalysis. Urinalysis did show characteristic findings, most notably glucosuria, increased beta2 microglobulin that were > or = 10 times that of normal levels, and increased N-acetylglucosaminidose levels in a high percentage of patients. Recurrent or exacerbating uveitis was seen in six patients (50%). In exacerbated or recurrent uveitis, inflammation was more severe (> or = 3+ cells of the anterior eye segment). The ocular inflammation generally responded well to treatment with oral corticosteroids, and the number of recurrences was lower at corticosteroid doses of > or = prednisolone 40 mg. CONCLUSIONS: Ophthalmologists play an important role in the initial discovery of patients with TINU syndrome. Because inflammation was more severe in exacerbated or recurrent uveitis, in instances where uveitis is refractory to local therapy, oral corticosteroids should be considered as early as possible.

Administration, Oral↗
PubMed2005

Expression of thymidine phosphorylase in choroidal malignant melanoma associated with neovascular glaucoma.

Reported herein is a case of 62-year-old man who complained of blurred vision and ocular pain in his right eye. The patient was diagnosed with choroidal melanoma complicated by neovascular glaucoma (NVG) and total retinal detachment, and he underwent enucleation of the eye. The isolated tumor was 2.5 x 2.5 cm in size. It was accompanied by intratumoral calcification, and consisted of epithelioid and spindle melanoma cells. There were a variety of microvessels in the stroma of the iris. The expression of thymidine phosphorylase (dThdPase), an angiogenic factor, was examined immunohistochemically. Cytoplasmic immunoreactivity for dThdPase was more prominent in the epithelioid cells than in spindle tumor cells. Another case of choroidal melanoma without NVG had less marked immunoreactivity. These results suggest that the production of dThdPase by melanoma cells correlates with the pathogenesis of NVG.

Biomarkers, Tumor↗
PubMed2005

Thrombospondin plays a vital role in the immune privilege of the eye.

PURPOSE: The role of thrombospondin (TSP)-1 in TGF-beta activation and T-cell suppression was studied in the retinal pigment epithelial (RPE) cells, a monolayer of pigmented cells that line the subretinal space, an immune-privileged site in the eye. METHODS: Posterior eyecups were prepared by excising the anterior segment, lens, and retina from enucleated eyes of C57BL/6, thrombospondin-1 knockout (TSP-1KO), and TGF-beta2 receptor II double-negative (TGF-beta2 RII DN) mice, leaving behind a healthy monolayer of RPE resting on choroid and sclera. Serum-free medium was added to these RPE eyecups, and, after various time intervals, supernatants (SNs) were removed and tested. RESULTS: SNs of an ex vivo culture of RPE cells from C57BL/6 mice were shown to inhibit both antigen and anti-CD3 activation of T cells, partially due to constitutive production of TGF-beta and to the ability of RPE to activate the latent form of TGF-beta. Activation of TGF-beta was entirely dependent on TSP-1, also produced by RPE. SNs of RPE from TSP-1KO mice failed to inhibit T-cell activation. Ovalbumin (OVA)-specific delayed hypersensitivity (DH) was not impaired when OVA was injected either into the subretinal space or into the anterior chamber of TSP-1KO mice before OVA immunization. Moreover, experimental autoimmune uveoretinitis was significantly more intense in eyes of TSP-1KO mice and failed to undergo spontaneous resolution unlike wild-type mice. CONCLUSIONS: Production of both TSP-1 and active TGF-beta by RPE is essential to the creation and maintenance of immune privilege in the subretinal space and that the immune privilege limits the severity and duration of retinal inflammation due to autoimmunity.

Animals↗
PubMed2005

Anti-inflammatory effects of aronia extract on rat endotoxin-induced uveitis.

PURPOSE: Aronia crude extract (ACE) with high levels of polyphenol compounds has been reported to have antioxidative effects in vitro and in vivo. In this study, attention was focused on the antioxidant effect of ACE. The purpose of the present study was to investigate the effect of ACE on endotoxin-induced uveitis (EIU) in rats. In addition, the endotoxin-induced expression of the inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 proteins was investigated in a mouse macrophage cell line (RAW 264.7) treated with ACE in vitro, to clarify the anti-inflammatory effect. METHODS: EIU was induced in male Lewis rats by a footpad injection of lipopolysaccharide (LPS). Immediately after the LPS inoculation, 1, 10, or 100 mg ACE or 10 mg prednisolone was injected intravenously. After 24 hours, the aqueous humor was collected from both eyes, and the number of infiltrating cells, protein concentration, nitric oxide (NO), prostaglandin (PG)-E2, and TNF-alpha levels in the aqueous humor were determined. RAW 264.7 cells treated with various concentrations of ACE were incubated with 10 mug/mL LPS for 24 hours. Levels of NO, PGE2, and TNF-alpha were determined by an enzyme-linked immunosorbent assay. The expression of iNOS and COX-2 proteins was analyzed by Western blot analysis. RESULTS: The number of inflammatory cells, the protein concentrations, and the levels of NO, PGE2, and TNF-alpha in the aqueous humor in the groups treated with ACE were significantly decreased in a dose-dependent manner. In addition, the anti-inflammatory effect of 100 mg ACE was as strong as that of 10 mg prednisolone. The anti-inflammatory action of ACE was stronger than that of either quercetin or anthocyanin administered alone. ACE also suppressed LPS-induced iNOS and COX-2 protein expressions in RAW 264.7 cells in vitro in a dose-dependent manner. CONCLUSIONS: The results suggest that ACE has a dose-dependent anti-ocular inflammatory effect that is due to the direct blocking of the expression of the iNOS and COX-2 enzymes and leads to the suppression of the production of NO, PGE2, and TNF-alpha.

Animals↗
PubMed2003

Increase of KL-6 in sera of uveitis patients with sarcoidosis.

BACKGROUND: KL-6 is a human glycoprotein secreted by type II alveolar cells in lung, and its serum levels increase in pneumonia of various causes. KL-6 is a member of the MUC-1 family, which is expressed in lung, cornea, and conjunctiva. The purpose of the present study was to investigate the clinical usefulness of quantifying serum KL-6 levels for diagnosing sarcoidosis in patients with uveitis. METHODS: Sera were obtained from 24 uveitis patients diagnosed with sarcoidosis, 37 uveitis patients with other etiologies, and 138 healthy control subjects. Serum concentration of KL-6 was determined by a human KL-6 electrochemiluminescence immunoassay. RESULTS: The average level of KL-6 in the sera of uveitis patients with sarcoidosis was 387 U/ml. This was significantly higher than in healthy subjects and uveitis patients with other etiologies. The KL-6 measurements identified 45.8% of sarcoidosis-positive patients. When the KL-6 results were combined with serum angiotensin-converting enzyme (ACE) concentrations, 87.5% of sarcoidosis patients were identified, compared to 66.7% using ACE results alone. The combined measurement identified 10.8% of the non-sarcoid patients and 0.72% of healthy subjects as positive (false positive). CONCLUSION: Combined measurements of serum KL-6 and ACE may be useful as a screening for sarcoidosis in uveitis patients.

Antigens↗
PubMed2002

Macrophage migration inhibitory factor in uveitis.

To summarize, we found that high levels of MIF were detected in the serum of uveitis patients with Behçet's disease, VKH disease, and sarcoidosis, as well as idiopathic iridocyclitis. In Behçet's disease and sarcoidosis, the MIF levels were higher in the active uveitis stage than in the inactive stage. Serum MIF increased after corticosteroid therapy in VKH disease. A high aqueous humor MIF concentration was detected at the onset of EAU. Finally, anti-MIF antibody suppressed EAU when administered in the early phase. MIF is thought to be an important cytokine in the pathogenesis of uveitis.

Humans↗
PubMed2002

Induction of regulatory T cells by the immunomodulating cytokines alpha-melanocyte-stimulating hormone and transforming growth factor-beta2.

Recently, we have reported that the cytokines alpha-melanocyte-stimulating hormone (alpha-MSH) and transforming growth factor-beta2 (TGF-beta2) work in synergy to induce the activation of regulatory T (Treg) cells. When we used alpha-MSH and TGF-beta2 to generate ocular autoantigen-specific Treg cells and adoptively transferred them into mice susceptible to experimental autoimmune uveoretinitis (EAU), there was suppression in the incidence and severity of EAU. Specificity to a retinal autoantigen was required for the Treg cells to suppress EAU. When stimulated, these Treg cells produced TGF-beta1, and their production of interferon-gamma, interleukin (IL)-10, and IL-4 was suppressed. Also, the Treg cells are suppressed in their proliferative response. Our results demonstrate that alpha-MSH with TGF-beta2 induce Treg cells that can subdue a tissue-specific autoimmune response. This also promotes the possibility of using these immunomodulating cytokines to purposely induce antigen-specific Treg cells to prevent and suppress autoimmune disease.

Adoptive Transfer↗
PubMed2002

Diminution of experimental autoimmune uveoretinitis (EAU) in mice depleted of NK cells.

To evaluate the potential role of NK1.1 (CD161c) cells in autoimmune uveoretinitis, we treated experimental autoimmune uveoretinitis (EAU)-susceptible mice with anti-CD161c antibodies (PK136) to deplete natural killer (NK) cells. Injection of anti-CD161c antibodies deleted NK cells from the peripheral blood of EAU-susceptible mice. The T cell proliferative response against the ocular autoantigen K2 was not suppressed in mice treated with anti-CD161c antibody when compared with T cells from control mice. Although mice treated with anti-CD161c developed EAU, the clinical severity on days 17 and 19 after induction of EAU was significantly mild in anti-CD161c-treated mice compared with control mice. In addition, the histopathological severity of EAU was significantly milder in mice treated with anti-CD161c antibodies than controls 21 days after induction of EAU. Our results indicate that the severity of EAU is augmented by NK1.1(+) NK cells.

Animals↗