Role In Systemic Immune Responses Research Articles

Characterization of IgD and IgT with their expressional analysis following subtype II megalocytivirus vaccination and infection in rock bream (Oplegnathus fasciatus)

In this study, heavy chain genes of IgD and IgT were sequenced and characterized their gene expression in rock bream (Oplegnathus fasciatus). Rock bream (RB)-IgD cDNA is 3319 bp in length and encodes a leader region, variable domains, a μ1 domain, and seven constant domains (CH1–CH7). A membrane-bound (mIgT) and secretory form (sIgT) of RB-IgT cDNAs are 1902 bp and 1689 bp in length, respectively, and encode a leader region, variable domains, four constant domains (CH1–CH4) and C-terminus. Their predicted 3D-structure and phylogenetic relation were similar to those of other teleost. In healthy fish, RB-IgD and mIgT gene expressions were higher in major lymphoid organs and blood, while RB-sIgT gene was more highly expressed in midgut. IgT expressing cells were detected in melano-macrophage centers (MMC) of head kidney in immunohistochemistry analysis. Under immune stimulation in vitro, RB-IgD and IgT gene expressions were upregulated in head kidney and spleen cells by bovine serum albumin or a rock bream iridovirus (RBIV) vaccine. In vivo, their expressions were significantly upregulated in head kidney, blood, and gill upon vaccination. Especially, RB-mIgT gene expression in head kidney and blood was upregulated at day 3 after vaccination while upregulated at earlier time point of day 1 by challenge with RBIV. This may suggest that memory cells might be produced during the primary response by vaccination and rapidly proliferated by secondary immune response by viral infection. RB-sIgT gene expression was highly upregulated in peripheral blood in vaccinated fish after viral infection, indicating that IgT plays an important role in systemic immune response as well as mucosal immune system. Our findings provide information on the role of RB-IgT in adaptive immunity during vaccination and viral infection in the vaccinated fish.

The association of polymorphisms (rs2227981 and rs10204525) of PDCD1 gene with susceptibility to human T-cell leukemia virus type 1

Human T-cell leukemia virus type 1 (HTLV-1) is the first retrovirus as the causative agent of two serious diseases in human is known.Programmed cell death-1 (PD-1) is a regulatory protein that has an important role in immune system response and created exhaustion phenotype in T cells at chronic infections; therefore, it can impair anti-viral responses. Since the single nucleotide polymorphisms (SNP) in PD-1gene may influence infection with HTLV-1virus, so in this research, association between SNPs in exon 5 of PD-1 gene with susceptibility to HTLV-1 infection and proviral load (PVL) in Iran's population studied. In this case-control study, PD-1 rs2227981 and rs10204525 polymorphisms were evaluated in 81 HTLV-1 asymptomatic carriers (ACs) and 162 healthy individuals (control groups). These polymorphisms were genotyped by Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Moreover, PVL was detected by quantitative real-time PCR (Q-RT-PCR). The results indicated that frequency of GA and AA genotypes in rs10204525 polymorphism was higher in ACs group (82.7%) than control group (26.5%) significantly; and GA + AA genotypes were significantly associated with HTLV-1 infection (OR = 13.244, 95%CI = 6.755–25.968, p = 0.000); but CT + TT genotypes in rs2227981 polymorphism, were as a protective factor against HTLV-1 infection (OR = 0.473, 95%CI = 0.279–0.813, P = 0.009). However, there was no significant difference between these polymorphisms and HTLV-1 PVL.

Corneal lymphangiogenesis ameliorates corneal inflammation and edema in late stage of bacterial keratitis

Lymphatic vessels play a crucial role in systemic immune response and regulation of tissue fluid homeostasis. Corneal lymphangiogenesis in bacterial keratitis has not been studied. In this study, we investigated the mechanism and the role of corneal lymphangiogenesis in a murine bacterial keratitis model using Pseudomonas aeruginosa. We first demonstrated that corneal lymphangiogenesis was enhanced mainly in the late stage of bacterial keratitis, contrary to corneal angiogenesis that started earlier. Corresponding to the delayed lymphangiogenesis, expression of the pro-lymphangiogenic factors VEGF-C and VEGFR-3 increased in the late stage of bacterial keratitis. We further found that F4/80 and CD11b positive macrophages played an essential role in corneal lymphangiogenesis. Notably, macrophages were specifically involved in corneal lymphangiogenesis in the late stage of bacterial keratitis. Finally, we demonstrated the beneficial role of corneal lymphangiogenesis in ameliorating the clinical course of bacterial keratitis. Our study showed that bacterial activity was not directly involved in the late stage of keratitis, while corneal lymphangiogenesis reduced corneal edema and clinical manifestation in the late stage of bacterial keratitis. These findings suggest that the process of lymphangiogenesis in bacterial keratitis ameliorates corneal inflammation and edema in the late stage of bacterial keratitis.

A high number of stromal tumor-infiltrating lymphocytes is a favorable independent prognostic factor in M0 (stages I-III) esophageal squamous cell carcinoma.

Esophageal cancer is a highly invasive tumor with a poor prognosis. Lymphocytes play an important role in systemic immune responses, but their role in cancers varies depending on the specific tumor microenvironment. The aim of this study was to provide evidence for tumor-infiltrating lymphocytes (TILs) as a prognostic biomarker in esophageal squamous cell carcinoma. TIL analysis was retrospectively performed on full-face hematoxylin and eosin-stained sections from 127 patients. A majority (92.6%) of tumors had at least 10% stromal TILs (sTILs) (range, 10%-90%), and 84.3% of cancers had at least 10% intraepithelial TILs (iTILs) (range, 10%-40%). Multivariate analysis showed progressively better overall survival (P<0.001, hazard ratio=0.968, 95% confidence interval 0.955-0.981) and disease-free survival (P=0.005, hazard ratio=0.982, 95% confidence interval 0.970-0.995) in patients with higher sTILs. Marginal increases in overall survival and disease-free survival were found in the higher iTILs cohort versus the lower iTILs cohort, but the difference was not significant. In conclusion, in addition to tumor stage increasing stromal lymphocytic infiltration is an independent prognostic factor for esophageal squamous cell carcinoma treated by radical resection.

Abstract P3-01-04: Differential Gene Expression Analysis among Post-Menopausal Caucasian Invasive Breast Cancer, Benign and Normal Subjects

Abstract Background: Breast Cancer (BC) is the second leading cause of cancer death among women in United States. There have been studies aiming to develop a blood-based BC detection assay, but most were focused on comparing blood samples between BC and normal subjects. Including benign disease patients in the study is critical in developing a BC detection assay. In addition, BC is a heterogeneous disease with distinct characteristics being associated with ethnicity and menopausal status. Thus we designed a study to analyze gene expression, in peripheral blood samples from invasive BC, benign disease and normal subjects, stratified by menopausal status and ethnicity. Here we report the results from Caucasian postmenopausal women. Method: Subjects were selected from the Clinical Breast Care Project (CBCP). Microarray data using Affymetrix GeneChip Human Genome U133 plus 2.0 arrays, of peripheral blood samples from pathologically confirmed invasive BC (n= 17) and benign patients (n= 17) were compared to those from normal subjects (n=17). All subjects were postmenopausal Caucasian women, matched for age. Using GenespringGX 11.0 software, the data were normalized, and QC on hybridization and internal controls were performed before filtering out probesets with the lowest 20% signal intensity in each array. Asymptotic t-test with FDR correction was used and significant pathways were obtained. Results: Comparison of gene expression in invasive BC patients (mean±SD = 63.7±7.0 years old) vs. normal subjects (mean±SD = 63.2±7.4 years) identified 1102 significantly different genes, satisfying the thresholds of corrected p &amp;lt; 0.05 and Fold Change (FC) &amp;gt; 1.5. Of them, 1003 genes were up regulated and 99 genes were down regulated in BC patients. Comparison of gene expression in benign disease women (mean±SD = 61.4±10.4 years) vs. normal women showed 1320 significantly different genes (corrected p &amp;lt; 0.05, FC &amp;gt; 1.5), with 1121 genes being up regulated and 199 genes being down regulated in benign patients. Of the top 10 genes with highest FC values, 6 genes (MBNL1, FAR1, MDM4, ITGA4, RAB8B, and EXOC5) were common in both analyses and were up regulated. NOTCH pathway was up regulated in both benign (p=0.038) and invasive (p=0.042) groups. Similarly, IL-7 pathway was up regulated in both benign (p=0.047) and invasive (p=0.030) patients. TCR pathway (p=7.36E-04) was up regulated in benign group only. The benign vs. invasive BC subjects did not show significant differential gene expression. Discussion: Our results provide a list of differentially expressed genes that are mostly up regulated in invasive and benign patients vs. normal subjects. NOTCH pathway is involved in cell-cell communication and angiogenesis. IL7 pathways play an important role in immune system response, cell proliferation and cell survival signaling. TCR pathway is highly significant only in benign patients and stimulation of TCR pathway induces a signaling cascade that ultimately results in activation of induced cell death. This activation could be early body response to prevent cancer development in benign subjects. When more microarray analyses are completed for this study, we hope to obtain a better understanding of the possibility of developing a blood-based BC detection assay. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-01-04.