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At least 721 records · Page 40Linked to original sources
PubMed2005

Construction and validation of a Bovine Innate Immune Microarray.

BACKGROUND: Microarray transcript profiling has the potential to illuminate the molecular processes that are involved in the responses of cattle to disease challenges. This knowledge may allow the development of strategies that exploit these genes to enhance resistance to disease in an individual or animal population. RESULTS: The Bovine Innate Immune Microarray developed in this study consists of 1480 characterised genes identified by literature searches, 31 positive and negative control elements and 5376 cDNAs derived from subtracted and normalised libraries. The cDNA libraries were produced from 'challenged' bovine epithelial and leukocyte cells. The microarray was found to have a limit of detection of 1 pg/microg of total RNA and a mean slide-to-slide correlation co-efficient of 0.88. The profiles of differentially expressed genes from Concanavalin A (ConA) stimulated bovine peripheral blood lymphocytes were determined. Three distinct profiles highlighted 19 genes that were rapidly up-regulated within 30 minutes and returned to basal levels by 24 h; 76 genes that were up-regulated between 2-8 hours and sustained high levels of expression until 24 h and 10 genes that were down-regulated. Quantitative real-time RT-PCR on selected genes was used to confirm the results from the microarray analysis. The results indicate that there is a dynamic process involving gene activation and regulatory mechanisms re-establishing homeostasis in the ConA activated lymphocytes. The Bovine Innate Immune Microarray was also used to determine the cross-species hybridisation capabilities of an ovine PBL sample. CONCLUSION: The Bovine Innate Immune Microarray has been developed which contains a set of well-characterised genes and anonymous cDNAs from a number of different bovine cell types. The microarray can be used to determine the gene expression profiles underlying innate immune responses in cattle and sheep.

Animals↗
PubMed1997

Primary and secondary infections by human parvovirus B19 following bone marrow transplantation: characterization by PCR and B-cell molecular immunology.

Due to the preparative regimen necessary, bone marrow transplantation (BMT) consistently results in severe immunodeficiency, often associated with anaemia, leukopenia and thrombocytopenia. Parvovirus B19 replicates in red blood cell precursors in the bone marrow and causes erythema infectiosum ('fifth disease'), anaemia, arthritis and foetal death. We assessed the significance of B19 infections as a cause of post-BMT complications. Over 900 serial serum samples from 201 allogeneic bone marrow recipients were studied by polymerase chain reaction (PCR) and by modern serodiagnostic methods. During the first 6 months after transplantation all BMT recipients remained B19 PCR-negative. Antibody screening for B19 infections was performed up to 36 months post-transplantation. Three cases of acute B19 infection were diagnosed during the second year post-BMT. To characterize the adoptively transferred immune system we measured subclasses and avidity of anti-VP1 IgG and epitope-type specificity (ETS) of anti-VP2 IgG, which allowed functional differentiation of primary and secondary B-cell responses long after BMT. The profile of the immune response was that of a primary infection in 1 and of reinfection in 2 of the 3 acute cases. Both types were clinically mild. Infection by human parvovirus B19 is not a frequent cause of post-BMT cytopenias. The findings with the new B19 antibody markers support the concept that the donated marrow determines the type of antiviral B-cell responses.

Adult↗
PubMed2006

An in vitro coculture model to study cytokine profiles of natural killer cells during maternal immune cell-trophoblast interactions.

OBJECTIVES: The cytokine milieu at the implantation site plays a role in human pregnancy. Th2 cytokines, such as interleukin (IL)-4 and IL-10, stimulate growth and development of placenta, whereas Th1 cytokines, such as tumor necrosis factor-alpha (TNF-alpha), are associated with pregnancy complications. Natural killer (NK) cells predominate at the implantation site. The aim of the present study is to investigate cytokine expression in NK cells when they are in close contact with JEG-3 trophoblast-like cells using an in vitro coculture model. METHODS: Female peripheral blood mononuclear cells (PBMCs) were cocultured with JEG-3 cells for 24 hours. PBMCs were harvested from the cocultures and stimulated with 25 ng/mL phorbol myristate acetate and 1 micromol/mL ionomycin in the presence of 2 micromol/mL monensin. NK cells were analyzed by flow cytometry for intracellular TNF-alpha, interferon-gamma (IFN-gamma), and IL-4 and IL-10 cytokines. Controls were PBMCs cultured without JEG-3 cells. RESULTS: The proportion of CD56+/TNF-alpha(+) NK cells was significantly decreased when they were in coculture with JEG-3 cells (26.1%) as compared to without JEG-3 cell coculture (40.8%) (P < .05). There was no difference in the proportion of CD56(+) NK cells expressing intracellular IFN-gamma, IL-4, and IL-10. Down-regulation of CD56+/TNF-alpha(+) NK cell levels was dependent on direct cell-to-cell contact between NK cells and JEG-3 cells. The expression of human leukocyte antigen (HLA)-G on trophoblast cell lines did not affect CD56+/TNF-alpha(+) NK cell levels under these experimental conditions. CONCLUSION: We report that JEG-3 cells induce down-regulation of intracellular CD56+/TNF-alpha(+) NK cell levels. It is speculated that trophoblasts may secure themselves from NK cell cytotoxicity via this mechanism.

Cell Communication↗
PubMed1996

Integrative neuroimmunology of the digestive tract.

The epithelium of the gastrointestinal tract is continuously exposed to the external environment containing food antigens, microbes and other pathogens. Immunologic and nonimmunologic mechanisms contribute to the neutralization and elimination of these foreign antigens. The immune system of the intestine is the most extensive in the organism and involves diffuse populations of immune cells, lymphoid aggregates and intraepithelial lymphocytes. On the other hand, the functions of the digestive tract contribute to the overall host defense (mucus secretion, gastric acid secretion, water and electrolyte secretion and peristaltism). These functions are regulated by intrinsic and extrinsic nervous systems. It is currently recognized that the physiological and pathological responses of the intestine require an integrate neuroimmune network. Such neuroimmune regulation is based on anatomical and biochemical supports. Indeed, there are membrane-to-membrane contacts between axonal varicosities and the immune cells. Specific receptors for neurotransmitters such as substance P, vasoactive intestinal polypeptide and somatostatin have been identified in many immune cells. Nerve profile change has been described under pathological conditions such as parasitic infections and acute phase of inflammation. In addition to supporting the growth and survival of several populations of nerves the classical nerve growth factor (NGF) has been shown to affect an immune cell population by inducing mast cell hyperplasia. Furthermore the NGF can induce mast cell degranulation, acting directly on mast cell membrane NGF receptors or indirectly by NGF-mediated release of substance P by peripheral extrinsic or intrinsic nerves. Moreover, non-immune cells such as epithelial and smooth muscle cells can produce immunologic messengers under pathological conditions such as infectious diseases or inflammation. Besides the local regulation of gut functions, neuroimmune control can be exerted at extra-intestinal sites. During physiological and pathological conditions, gastrointestinal secretions and motor events are strongly regulated by the central nervous system. Moreover, infectious agents can induce cytokine and particularly interleukin-1 release by the brain astrocytes and microglial cells which have been shown to play a pivotal role in fever induction and modifications of the gastrointestinal functions. Visceral afferent fibers play a pivotal role in 'cross-communication' between central sites and immune response. Recent studies evoke, more specifically, the role of vagus as a key modulatory participant in the close relationship between the extraintestinal nerves and the immune system. Future work in this field will clarify the role of the different participants in the intimate communication between the gastrointestinal tract, immune system and central nervous system.

Animals↗
PubMed1998

[Critical involvement of the specific neuroendocrine profile for an adequate T-dependent immune response].

A functional relationship between the neuroendocrine and immune systems has been clearly established. We examined the role of neuroendocrine changes, particularly thyrotropin-releasing hormone (TRH) and prolactin (PRL), during the T cell-dependent immune response. After immunization of rats with sheep red blood cells (SRBC, a T cell-dependent antigen) we observed: a) an increase of hypothalamic TRH mRNA at 4 to 24 h post-immunization (i.e.: SRBC vs saline: 4 h, 2.8x), in contrast to the decrease of TRH mRNA observed following treatment with LPS, a T-independent antigen (LPS vs saline: 4 h, 1.6x); b) an increase in pituitary TRH receptor mRNA and plasma PRL levels but no changes in thyroid-stimulating hormone and growth hormone plasma levels. Intracerebroventricular (icv) injection in conscious freely-moving rats of antisense oligonucleotide complementary to rat TRH mRNA resulted in: a) a significant inhibition of specific antibody production [ELISA 7 days: Ig(M/G): TRH sense vs TRH-antisense: 384 +/- 27 (n = 11) vs 193 +/- 22 (n = 11); p < 0.001]b) an inability to produce the peak in plasma PRL levels in rats immunized with SRBC [(12h post-immunization, TRH-sense vs TRH-antisense: 8.3 +/- 1.4 (n = 6) vs 2.2 +/- 0.5 (n = 6); p < 0.01]; c) a decrease in hypothalamic TRH mRNA (TRH-sense vs TRH-antisense: 12h, 1.7x). These studies demonstrate that the T-cell antigen needs an early activation of TRH and PRL for an adequate immune response, in contrast to the inhibition induced by a T-cell independent antigen.

Analysis of Variance↗
PubMed1996

Dendritic cells in antitumor immune responses. II. Dendritic cells grown from bone marrow precursors, but not mature DC from tumor-bearing mice, are effective antigen carriers in the therapy of established tumors.

Antitumor CTL responses were studied in a model tumor hearing a mutant human p53 gene. We found ineffective induction of antitumor CTL in mice bearing these tumors associated with measurable defects in the function of dendritic cells (DC) from these animals. In this study we investigate the mechanism of this defect in mature DC and find that functional DC can be generated by growth from the bone marrow of tumor-hearing animals. Tumor cell supernatants did not affect the function of mature DC obtained from the spleen of tumor-bearing animals, but significantly suppressed the ability to generate functional DC from the bone marrow of control mice in vitro. This suggests that tumor cells may release factors which block early stages of DC maturation from precursors. DC generated from the bone marrow of tumor-bearing mice showed normal potential to stimulate allogeneic T cells, to stimulate anti-mutant p53 peptide-specific cytotoxic T cells, and to induce anti-p53 CTL responses in vivo in control mice. Repeated immunization with peptide-pulsed DC generated from the bone marrow of control mice (every 4-5 days) blocked progression of established tumors. Immunization of mice with peptide-pulsed DC obtained from the spleen of tumor-bearing mice (4 weeks after tumor injection) did not affect the tumor growth, whereas immunization with peptide-pulsed DC generated from bone marrow of tumor-bearing mice resulted in significantly prolonged survival and delayed tumor growth. Tumor progression was associated with change of the balance Th1/Th2 cells in favor of the Th2-like cytokine profile, while effective immunization was associated with a shift to the Th1 phenotype. Thus, frequent immunization of mice with mutant p53 peptide-pulsed DC generated from stem cells of tumor-bearing hosts can induce effective antitumor CTL responses associated with production of Th1 cells and lead to significant antitumor effects.

Amino Acid Sequence↗
PubMed1977

The nature of the local immune system of the bovine mammary gland.

The origin of the immunoglobulins of bovine colostrum and milk were examined by using radiolabeled protein. Colostrum was found to consist mainly of immunoglobulin derived from serum, although there was some local synthesis. In lactation the immunoglobulins of milk were almost entirely serum derived. The local immune system was very inactive but could be stimulated to activity by local immunization. The immunoglobulin profiles of the secretion from the stimulated gland were still relatively deficient in IgA compared to other species, notably the pig.

Animals↗
PubMed2025

The MTORC1 signaling pathway related gene POLR3G serves as a potential prognostic biomarker in Hepatocellular Carcinoma.

This study aims to investigate the prognostic significance and potential biological functions of the MTORC1 signaling pathway-associated gene POLR3G in Hepatocellular carcinoma (HCC). A prognostic risk model for HCC was developed by integrating HCC-related datasets and associated clinical data obtained from The Cancer Genome Atlas (TCGA) database. The GSVA website was employed to analyze the model genes across pan-cancer datasets, focusing on copy number variations (CNV), single nucleotide variations (SNV), methylation differences, drug sensitivity and immune cell infiltration profiles. Subsequently, we examined the expression levels and prognostic significance of POLR3G in HCC. Utilizing Spearman correlation analysis, we identified genes associated with POLR3G. Furthermore, Gene Set Enrichment Analysis (GSEA) was employed to elucidate the potential signaling pathways in which POLR3G may be involved. The relationship between POLR3G expression and immune cell abundance in HCC samples was assessed using the ssGSEA algorithm. Finally, the impact of POLR3G on HCC cell proliferation was validated through CCK-8 and EDU cell proliferation assays. Through univariate Cox regression analysis and LASSO regression analysis, we established a prognostic risk model for HCC comprising 13 genes. The analysis revealed that individuals categorized in the low-risk group had a markedly improved overall survival probability relative to those in the high-risk group. POLR3G exhibited a markedly elevated expression in HCC tissues when compared to adjacent normal tissues. The expression of POLR3G was correlated with tumor grade, and elevated POLR3G expression was associated with poor prognosis in HCC patients. Furthermore, the expression level of POLR3G was found to be correlated with the level of immune cell infiltration. Knockdown of POLR3G significantly inhibited the proliferative capacity of hepatocellular carcinoma cells. The findings suggest that POLR3G may serve as a potential biomarker influencing the prognosis of hepatocellular carcinoma patients by modulating the tumor immune microenvironment.

Humans↗
PubMed2004

Regulation of the Mycobacterium tuberculosis PE/PPE genes.

The genome of Mycobacterium tuberculosis encodes approximately 170 members of the unique mycobacterial PE and PPE gene families. Evidence suggests members of these families are surface-associated cell wall proteins that may provide a diverse antigenic profile and affect immunity. To determine if the expression patterns of PE/PPE genes are consistent with a role in antigenic variability, we analyzed microarray data from 132 experimental conditions for expression of PE/PPE genes. Whole genome expression patterns show that the PE/PPE genes are regulated in a variable and largely independent manner. Gene expression profiling of 15 unique conditions identified differential regulation of 128 of the 169 PE/PPE genes. Expression of the PE/PPE genes appears to be controlled by a variety of independent mechanisms. These data indicate that differential expression of the PE/PPE genes has the potential to provide a dynamic antigenic profile during the course of changing microenvironments within the host.

Antigenic Variation↗
PubMed2005

Airway generation-specific differences in the spatial distribution of immune cells and cytokines in allergen-challenged rhesus monkeys.

BACKGROUND: Accumulation of immune cell populations and their cytokine products within tracheobronchial airways contributes to the pathogenesis of allergic asthma. It has been postulated that peripheral regions of the lung play a more significant role than proximal airways with regard to inflammatory events and airflow obstruction. OBJECTIVE: To determine whether immune cell populations and associated cytokines are uniformly distributed throughout the conducting airway tree in a non-human primate model of allergic asthma. METHODS: We used a stereologic approach with a stratified sampling scheme to measure the volume density of immune cells within the epithelium and interstitium of trachea and 4-5 intrapulmonary airway generations from house dust mite (HDM) (Dermatophagoides farinae)-challenged adult monkeys. In conjunction with immune cell distribution profiles, mRNA levels for 21 cytokines/chemokines and three chemokine receptors were evaluated at four different airway generations from microdissected lungs. RESULTS: In HDM-challenged monkeys, the volume of CD1a+ dendritic cells, CD4+ T helper lymphocytes, CD25+ cells, IgE+ cells, eosinophils, and proliferating cells were significantly increased within airways. All five immune cell types accumulated within airways in unique patterns of distribution, suggesting compartmentalized responses with regard to trafficking. Although cytokine mRNA levels were elevated throughout the conducting airway tree of HDM-challenged animals, the distal airways (terminal and respiratory bronchioles) exhibited the most pronounced up-regulation. CONCLUSION: These findings demonstrate that key effector immune cell populations and cytokines associated with asthma differentially accumulate within distinct regions and compartments of tracheobronchial airways from allergen-challenged primates.

Animals↗
PubMedDate not supplied

[Initial antiretroviral prescriptions in patients with HIV. Second semester 1994-second semester 1996].

OBJECTIVES: The nature of antiretroviral therapy has radically changed these last years. A study has been conducted on data obtained from the DMI2 information system to evaluate changes on treatments, immunity and transmission profile of the patient naive to antiretroviral therapy when initiating a therapy. METHODS: DMI2 is a national, multicentered database which contains medical, epidemiological and economic information on hospital care for HIV patients. This study, on 18,510 patients followed up in one of the fifty hospitals belonging to the Centers for Information and Care of Human immune Deficiency, was conducted from the second half of 1994 to the second half of 1996. RESULTS: The therapeutic changes seen on the whole seropositive population are also observed on these patients: the proportion of regimen with only one nucleoside analogue have decreased from 90.2% in 1994 to 7.5% in 1996. The proportion of treatment with two nucleoside analogues increased from 7.9% to 67.6%. The proportion of two nucleoside analogues with one protease inhibitor regimen increased from 1.9% in 1994 to 24.6% at the end of 1996. A study focused on the second semester of 1996 shows that the proportion of homo-bisexual patients initiating an antiretroviral treatment with a three antiretroviral agents combination (29.7%) is greater than the one in the IVDU group (20.4%) or in the heterosexual group (20.8%). CONCLUSION: These results show that a higher number of patient naive to the antiretroviral therapy initiate therapy earlier, with a two or three agents combination preferentially and at a better stage of immunity.

Anti-HIV Agents↗
PubMed1980

Evaluation of different methods for detecting circulating immune complexes. An inter-laboratory study.

Forty serum samples of healthy blood donors and 60 sera of SLE patients were tested in parallel by 7 different assays for detecting immune complexes. Significantly higher titres and significant higher incidence of positive results were observed in the patient group than in the control group in 6 tests. No test discriminated between patients in an active stage of the disease and those whose disease was inactive. Significantly higher immune complex levels were found in lupus nephritis than in the non-nephritic patients by the complement consumption test. Significant positive correlation was obtained between the results of the macrophage aggregated IgG uptake inhibition and PEG-precipitation tests and between two tests based on the interaction of the complexes with the complement system. A characteristic 'profile' of the immune complex assay was observed in the course of the repeated testings of the same patients. The results indicate that the different methods detect different types of immune complexes present in the blood of the patients.

Antigen-Antibody Complex↗
PubMed2006

Induction of antigen-specific immune responses in vivo after vaccination with dendritic cells transduced with adenoviral vectors encoding hepatitis C virus NS3.

Dendritic cells (DC) are potent antigen-presenting cells that play a critical role in the initiation of immunity to viral infections. Direct transduction of DC appears to be the major pathway in vivo responsible for induction of antigen specific immune responses. The aim of this study was to explore the vaccine potential of DC transduced with adenoviral vectors encoding the HCV nonstructural protein 3 (AdNS3) compared to DC pulsed with recombinant NS3 (rNS3). Mice (Balb/c and C57BL/6 transgenic for HLA-A2.1) were immunized with DC based vaccines. After the immunization, antigen specific immune responses including humoral responses, cytokine secretion, and IFN-gamma-producing T cell responses were analyzed. In both strains of mice inoculated with DC transduced with an adenovirus, the generated NS3 specific antibody response and IFN-gamma-secreting T cell response were stronger than that generated by rNS3-pulsed DC. Analysis of the cytokine profiles revealed that immunization with AdNS3 transduced DC shifted the antigen specific immunity towards Th1 responses. DC transduced with AdNS3 are superior to DC pulsed with rNS3 in inducing vigorous humoral and Th1-type cellular responses against NS3. The results demonstrate for the first time the immunogenic potential of genetically modified DC by a prime and boost approach in eliciting a strong NS3-specific, cell-mediated, humoral immune response in both Balb/c mice and HLA-A2.1 transgenic mice.

Adenoviridae↗
PubMed2000

Ongoing murine T1 or T2 immune responses to the hepatitis B surface antigen are excluded from the liver that expresses transgene-encoded hepatitis B surface antigen.

Different protein- or DNA-based vaccination techniques are available that prime potent humoral and cellular, T1 or T2 immune responses to the hepatitis B surface Ag (HBsAg) in mice. T1 and T2 are immune responses with isotype profile indicating Th1 and Th2 immunoregulation. We tested whether HBsAg-specific immune responses can be established in transgenic mice that express HBsAg in the liver (HBs-tg mice) using either these different vaccination techniques or an adoptive transfer system. HBsAg-specific responses could not be primed in HBs-tg mice with the established, potent vaccine delivery techniques. In contrast, adoptive transfers of T1- and T2-type HBsAg-immune spleen cells into congenic HBs-tg hosts (that were not conditioned by pretreatment) suppressed HBsAg antigenemia and gave rise to HBsAg-specific serum Ab titers. The establishment of continuously rising anti-HBsAg serum Ab levels with alternative isotype profiles (reflecting T1 or T2 polarization) in transplanted HBs-tg hosts required donor CD4+ T cell-dependent restimulation of adoptively transferred immune cells by transgene-derived HBsAg. Injections of HBsAg-specific Abs into HBs-tg mice did not establish stable humoral immunity. The expanding T1 or T2 immune responses to HBsAg in HBs-tg hosts did not suppress transgene-directed HBsAg expression in the liver and did not induce liver injury. In addition to priming functional antiviral effector cells, the conditioning of the liver microenvironment to enable delivery of antiviral effector functions to this organ are therefore critical for effective antiviral defense. A major challenge in the development of a therapeutic vaccine against chronic hepatitis B or C virus infection is thus the efficient targeting of specifically induced immune effector specificities to the liver.

Adoptive Transfer↗
PubMed1987

Combined evaluation of circulating immune complexes and antibodies to Pseudomonas aeruginosa as an immunologic profile in relation to pulmonary function in cystic fibrosis.

We developed a solid-phase radioimmunoassay with a reference standard pseudomonas antigen and used this with 125I-labeled anti-human immunoglobulin to evaluate specific antibodies to Pseudomonas aeruginosa, qualitatively and quantitatively, in sera from children with cystic fibrosis (CF) whose lungs were colonized by this bacterium. The results of this IgG assay correlated with the number of precipitin antibodies to the standard reference antigen determined by cross-immunoelectrophoresis in the same sera. Forced expiratory volume (FEV1; percentage predicted), determined as an indicator of lung injury in CF, was evaluated as an immunologic response to pseudomonas, against a profile derived from combined serial data on both the circulating immune complexes (CIC) and the Ps. aeruginosa antibodies (N = 25 CF patients; 108 sera). This revealed that in CF patients who had no specific IgG antibodies to Ps. aeruginosa and no IgG-CIC had the best pulmonary function (FEV1 = 115 +/- 14.52%) and those with high levels of antibodies to this organism and high IgG-CIC levels had the poorest lung function (FEV1 = 69.75 +/- 10.99%) (P less than 0.05). We believe that this indicates an immunologic basis for lung injury in cystic fibrosis.

Antibodies, Bacterial↗
PubMed1994

Behavioral and immunological events induced by electrical stimulation of the rat midbrain periaqueductal gray region.

We report here on the immunological and behavioral alterations induced by stimulation of the mesencephalic periaqueductal gray matter (PAG), a component of the brain aversive system. Male Wistar rats were implanted with stimulating electrodes in the caudal dorsolateral part of the PAG. After recovery, animals were screened for aversive behavior, characterized by running, jumping, vocalization or freezing reaction. Then, rats were subdivided to those which could control aversive stimulation (AS) by switch-off response (cAS group) and those which could not interrupt AS (uAS group). After sensitization with bovine serum albumin (BSA) in complete Freund's adjuvant, rats were stimulated 3 times/week for 40 days, each session lasting 30 min/rat. Immunological assessment included antibody production and hypersensitivity skin reactions to BSA 14 and 21 days after immunization. A behavioral profile of aversively stimulated animals was determined by a poststartle response, open field (OF) activity and two-way shuttle-box avoidance task. The results revealed elevated antibody production to BSA in cAS and lowered in uAS rats, compared to sham-stimulated and intact controls. Arthus and delayed hypersensitivity skin reactions increased in PAG-stimulated animals on day 14 but not on day 21 after immunization. Poststartle response was enhanced both in cAS and uAS rats. Along with immunopotentiation, administration of cAS produced hyperactivity in OF test and facilitation of the active avoidance learning, whereas uAS caused only moderate suppression of rearing in a novel OF environment. Physiological implications and possible mechanisms that may account for PAG-mediated immunobehavioral changes are outlined.

Animals↗
PubMed2004

Gene expression profiling in type 1 diabetes prone NOD mice immunized with a disease protective autoantigenic peptide.

Immunization with autoantigenic peptides skews T cell responses in type 1 diabetes (T1D), yet the gene-expression signature characterizing this change is unclear. We used cDNA microarray technology to identify genes differentially regulated in splenocytes of T1D prone NOD mice after immunization with a disease protective glutamic acid decarboxylase 65 (GAD(65) P14) peptide. We identified 96 genes involved in cytokine secretion, humoral immune response, T cell activation, signal transduction, cell proliferation, complement activation and inflammatory responses. Up-regulation of seven chemokine and cytokine genes confirmed our previous findings of increased interferon-gamma (IFN-gamma) secretion, which may lead to a protective response in T1D. Hierarchical clustering was used to organize treated and control groups on the basis of their overall similarity in gene-expression patterns, suggesting association or co-regulation. Semi-quantitative RT-PCR was used to confirm the expression of selected genes in spleen and pancreatic draining lymph nodes. These findings can be used to compare other immunization strategies affecting the expression of these genes and explore their mechanisms of action. This microarray-based study, thus, unravels the molecular mechanism of beta-cell associated autoantigenic peptide immunization in T1D prone NOD mice, paving the way for identification of diagnostic markers and drug targets for modulating immune responses in T1D.

Animals↗