scholarly journals Prediction of IL4 Inducing Peptides

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Sandeep Kumar Dhanda ◽  
Sudheer Gupta ◽  
Pooja Vir ◽  
G. P. S. Raghava
Keyword(s):  
Mhc Class Ii ◽  
Critical Role ◽  
Interleukin 4 ◽  
Th2 Response ◽  
Data Set ◽  
T Helper 2 ◽  
Cell Responses ◽  
Antibody Class ◽  
First Time ◽  
Motif Information

The secretion of Interleukin-4 (IL4) is the characteristic of T-helper 2 responses. IL4 is a cytokine produced by CD4+ T cells in response to helminthes and other extracellular parasites. It has a critical role in guiding antibody class switching, hematopoiesis and inflammation, and the development of appropriate effector T-cell responses. In this study, it is the first time an attempt has been made to understand whether it is possible to predict IL4 inducing peptides. The data set used in this study comprises 904 experimentally validated IL4 inducing and 742 noninducing MHC class II binders. Our analysis revealed that certain types of residues are preferred at certain positions in IL4 inducing peptides. It was also observed that IL4 inducing and noninducing epitopes differ in compositional and motif pattern. Based on our analysis we developed classification models where the hybrid method of amino acid pairs and motif information performed the best with maximum accuracy of 75.76% and MCC of 0.51. These results indicate that it is possible to predict IL4 inducing peptides with reasonable precession. These models would be useful in designing the peptides that may induce desired Th2 response.

scholarly journals Transgenic Expression of CXCR3 on T Cells Enhances Susceptibility to Cutaneous Leishmania major Infection by Inhibiting Monocyte Maturation and Promoting a Th2 Response

2014 ◽  
Vol 83 (1) ◽  
pp. 67-76 ◽  
Author(s):  
Steve Oghumu ◽  
James C. Stock ◽  
Sanjay Varikuti ◽  
Ran Dong ◽  
Cesar Terrazas ◽  
...  
Keyword(s):  
T Cells ◽  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Critical Role ◽  
Sand Fly ◽  
Interleukin 4 ◽  
Th2 Response ◽  
Content Type ◽  
Transgenic Expression ◽  
Inflammatory Monocytes

Cutaneous leishmaniasis, caused mainly byLeishmania major, an obligate intracellular parasite, is a disfiguring disease characterized by large skin lesions and is transmitted by a sand fly vector. We previously showed that the chemokine receptor CXCR3 plays a critical role in mediating resistance to cutaneous leishmaniasis caused byLeishmania major. Furthermore, T cells fromL. major-susceptible BALB/c but notL. major-resistant C57BL/6 mice fail to efficiently upregulate CXCR3 upon activation. We therefore examined whether transgenic expression of CXCR3 on T cells would enhance resistance toL. majorinfection in susceptible BALB/c mice. We generated BALB/c and C57BL/6 transgenic mice, which constitutively overexpressed CXCR3 under a CD2 promoter, and then examined the outcomes withL. majorinfection. Contrary to our hypothesis, transgenic expression of CXCR3 (CXCR3Tg) on T cells of BALB/c mice resulted in increased lesion sizes and parasite burdens compared to wild-type (WT) littermates afterL. majorinfection. Restimulated lymph node cells fromL. major-infected BALB/c-CXCR3Tgmice produced more interleukin-4 (IL-4) and IL-10 and less gamma interferon (IFN-γ). Cells in draining lymph nodes from BALB/c-CXCR3Tgmice showed enhanced Th2 and reduced Th1 cell accumulation associated with increased neutrophils and inflammatory monocytes. However, monocytes displayed an immature phenotype which correlated with increased parasite burdens. Interestingly, transgenic expression of CXCR3 on T cells did not impact the outcome ofL. majorinfection in C57BL/6 mice, which mounted a predominantly Th1 response and spontaneously resolved their infection similar to WT littermates. Our findings demonstrate that transgenic expression of CXCR3 on T cells increases susceptibility of BALB/c mice toL. major.

scholarly journals Dectin-2 Deficiency Promotes Th2 Response and Mucin Production in the Lungs after Pulmonary Infection with Cryptococcus neoformans

2014 ◽  
Vol 83 (2) ◽  
pp. 671-681 ◽  
Author(s):  
Yuri Nakamura ◽  
Ko Sato ◽  
Hideki Yamamoto ◽  
Kana Matsumura ◽  
Ikumi Matsumoto ◽  
...  
Keyword(s):  
Cryptococcus Neoformans ◽  
Mhc Class Ii ◽  
Proinflammatory Cytokines ◽  
Fungal Pathogen ◽  
Fluorescent Protein ◽  
Yeast Cells ◽  
Interleukin 4 ◽  
Th2 Response ◽  
Content Type ◽  
Mucin Production

Dectin-2 is a C-type lectin receptor that recognizes high mannose polysaccharides.Cryptococcus neoformans, a yeast-form fungal pathogen, is rich in polysaccharides in its cell wall and capsule. In the present study, we analyzed the role of Dectin-2 in the host defense againstC. neoformansinfection. In Dectin-2 gene-disrupted (knockout) (Dectin-2KO) mice, the clearance of this fungus and the inflammatory response, as shown by histological analysis and accumulation of leukocytes in infected lungs, were comparable to those in wild-type (WT) mice. The production of type 2 helper T (Th2) cytokines in lungs was higher in Dectin-2KO mice than in WT mice after infection, whereas there was no difference in the levels of production of Th1, Th17, and proinflammatory cytokines between these mice. Mucin production was significantly increased in Dectin-2KO mice, and this increase was reversed by administration of anti-interleukin 4 (IL-4) monoclonal antibody (MAb). The levels of expression of β1-defensin, cathelicidin, surfactant protein A (Sp-A), and Sp-D in infected lungs were comparable between these mice. Inin vitroexperiments, IL-12p40 and tumor necrosis factor alpha (TNF-α) production and expression of CD86 and major histocompatibility complex (MHC) class II by bone marrow-derived dendritic cells and alveolar macrophages were completely abrogated in Dectin-2KO mice. Finally, the disrupted lysates ofC. neoformans, but not of whole yeast cells, activated Dectin-2-triggered signaling in an assay with nuclear factor of activated T cells (NFAT)-green fluorescent protein (GFP) reporter cells expressing this receptor. These results suggest that Dectin-2 may oppose the Th2 response and IL-4-dependent mucin production in the lungs after infection withC. neoformans, and it may not be required for the production of Th1, Th17, and proinflammatory cytokines or for clearance of this fungal pathogen.

scholarly journals T-Cell Responses to Immunodominant LACK Antigen Do Not Play a Critical Role in Determining Susceptibility of BALB/c Mice toLeishmania mexicana

2001 ◽  
Vol 69 (1) ◽  
pp. 617-621 ◽  
Author(s):  
Fabiola Aguilar Torrentera ◽  
Nicolas Glaichenhaus ◽  
Jon D. Laman ◽  
Yves Carlier
Keyword(s):  
T Cells ◽  
T Cell ◽  
Leishmania Major ◽  
Critical Role ◽  
Interleukin 4 ◽  
Hybridoma Cells ◽  
Leishmania Mexicana ◽  
Wild Type ◽  
Cell Responses ◽  
Early Production

ABSTRACT Although BALB/c mice develop lesions when infected withLeishmania mexicana, the mechanisms which are responsible for susceptibility to this parasite have not been elucidated. In contrast, susceptibility of BALB/c mice to Leishmania majorhas been shown to depend on the early production of interleukin-4 (IL-4) by T cells which react to the parasitic LACK antigen. Here, we demonstrate that the lesions induced by L. mexicana are delayed compared to those induced by L. major but rapidly develop at later time points. Interestingly, while LACK-tolerant BALB/c-derived IE-LACK transgenic mice were resistant to L. major, they were susceptible to L. mexicana and developed lesions similar to those observed in wild-type BALB/c mice. The latter result was observed despite the fact that (i) LACK was expressed by L. mexicana, (ii) splenocytes from BALB/c mice were able to stimulate LACK-specific T-cell hybridoma cells when incubated with live L. mexicana promastigotes, and (iii) LACK-specific T cells contributed to IL-4 production in L. mexicana-infected BALB/c mice. Thus, in contrast to what was observed for L. major-infected mice, LACK-specific T cells do not play a critical role in determining susceptibility to L. mexicana. Although BALB/c mice are susceptible to both L. major and L. mexicana, the mechanisms which are responsible for susceptibility to these parasites are likely to be different.

scholarly journals Both Free-Living and Parasitic Nematodes Induce a Characteristic Th2 Response That Is Dependent on the Presence of Intact Glycans

2004 ◽  
Vol 72 (1) ◽  
pp. 398-407 ◽  
Author(s):  
Salah Tawill ◽  
Laetitia Le Goff ◽  
Fahimeda Ali ◽  
Mark Blaxter ◽  
Judith E. Allen
Keyword(s):  
Immune Response ◽  
Critical Role ◽  
Interleukin 4 ◽  
Parasitic Nematodes ◽  
Mammalian Host ◽  
Phylogenetic Distance ◽  
Th2 Response ◽  
Free Living ◽  
Th2 Immune Response

ABSTRACT Infection with parasitic nematodes is characterized by the induction of a profound type 2 immune response. We have studied the role of glycans in the induction of the skewed type 2 response by antigens of the parasitic nematode Brugia malayi as well as the free-living nematode Caenorhabditis elegans. Lymph node cells from BALB/c mice immunized with soluble extracts of the two nematodes showed distinct antigen-specific proliferation and cytokine production; however, both nematodes induced antigen-specific interleukin 4 (IL-4) production, demonstrating that the induction of a biased type 2 response is not unique to parasitic nematodes. Sodium periodate-treated soluble extracts of both nematodes consistently induced significantly less IL-4 production than the respective mock-treated extracts, indicating that glycans play a critical role in the induction of the Th2 immune response by these nematodes. The glycan-dependent induction of the Th2-potentiating cytokine IL-4 occurs by 72 h postinoculation. Our data suggest that glycan determinants common to nematodes act as ligands, displaying distinct molecular patterns that trigger the immune system to launch a biased Th2 immune response upon exposure to these organisms or their products. Further, the similarity of our findings to those for Schistosoma mansoni egg antigen is striking considering the enormous phylogenetic distance between nematodes and trematodes. These data thus have important implications for how the mammalian host responds to widely divergent metazoan invaders and suggest that the powerful C. elegans model system can be used to address these questions.

scholarly journals Hormonal Regulation of CD4+ T-Cell Responses in Coxsackievirus B3-Induced Myocarditis in Mice

1999 ◽  
Vol 73 (6) ◽  
pp. 4689-4695 ◽  
Author(s):  
S. A. Huber ◽  
J. Kupperman ◽  
M. K. Newell
Keyword(s):  
T Cells ◽  
T Cell ◽  
Hormonal Regulation ◽  
Cell Activation ◽  
Coxsackievirus B3 ◽  
Interleukin 4 ◽  
Th2 Response ◽  
Th1 Cell ◽  
Cell Responses

ABSTRACT Coxsackievirus B3 infection causes significant cardiac inflammation in male, but not female, B1.Tg.Eα mice. This gender difference in disease susceptibility correlates with selective induction of CD4+ Th1 (gamma interferon-positive) cell responses in animals with testosterone, whereas estradiol promotes preferential CD4+ Th2 (interleukin-4 positive [IL-4+]) cell responses. Differences in immune deviation of CD4+ T cells cannot be explained by variation in B7-1 or B7-2 expression. Infection significantly upregulated both molecules, but no differences were detected between estradiol- and testosterone-treated groups. Significantly increased numbers of activated (CD69+) T cells expressing the γδ T-cell receptor were found in male and testosterone-treated male and female mice. In vivo depletion of γδ+ cells by using monoclonal antibodies inhibited myocarditis and resulted in a shift from a Th1 to Th2 response phenotype. Taken together, our results indicate that testosterone promotes a CD4+ Th1 cell response and myocarditis by promoting increased γδ+ cell activation.

scholarly journals Inhibition of CRTH2-mediated Th2 activation attenuates pulmonary hypertension in mice

2018 ◽  
Vol 215 (8) ◽  
pp. 2175-2195 ◽  
Author(s):  
Guilin Chen ◽  
Shengkai Zuo ◽  
Juan Tang ◽  
Caojian Zuo ◽  
Daile Jia ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Critical Role ◽  
Th2 Cells ◽  
Th2 Response ◽  
T Helper 2 ◽  
Th2 Immune Response ◽  
Life Threatening ◽  
Pulmonary Arterial ◽  
Cell Expression ◽  
Cell Adoptive Transfer

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by progressive pulmonary artery (PA) remodeling. T helper 2 cell (Th2) immune response is involved in PA remodeling during PAH progression. Here, we found that CRTH2 (chemoattractant receptor homologous molecule expressed on Th2 cell) expression was up-regulated in circulating CD3+CD4+ T cells in patients with idiopathic PAH and in rodent PAH models. CRTH2 disruption dramatically ameliorated PA remodeling and pulmonary hypertension in different PAH mouse models. CRTH2 deficiency suppressed Th2 activation, including IL-4 and IL-13 secretion. Both CRTH2+/+ bone marrow reconstitution and CRTH2+/+ CD4+ T cell adoptive transfer deteriorated hypoxia + ovalbumin–induced PAH in CRTH2−/− mice, which was reversed by dual neutralization of IL-4 and IL-13. CRTH2 inhibition alleviated established PAH in mice by repressing Th2 activity. In culture, CRTH2 activation in Th2 cells promoted pulmonary arterial smooth muscle cell proliferation through activation of STAT6. These results demonstrate the critical role of CRTH2-mediated Th2 response in PAH pathogenesis and highlight the CRTH2 receptor as a potential therapeutic target for PAH.

scholarly journals Induction of Airway Mucus Production By T Helper 2 (Th2) Cells: A Critical Role For Interleukin 4 In Cell Recruitment But Not Mucus Production

1997 ◽  
Vol 186 (10) ◽  
pp. 1737-1747 ◽  
Author(s):  
Lauren Cohn ◽  
Robert J. Homer ◽  
Anthony Marinov ◽  
John Rankin ◽  
Kim Bottomly
Keyword(s):  
Airway Inflammation ◽  
Critical Role ◽  
Interleukin 4 ◽  
Th2 Cells ◽  
Direct Role ◽  
Mucus Production ◽  
Cell Recruitment ◽  
T Helper 2 ◽  
Asthmatic Patients ◽  
Th1 And Th2

Airway inflammation is believed to stimulate mucus production in asthmatic patients. Increased mucus secretion is an important clinical symptom and contributes to airway obstruction in asthma. Activated CD4 Th1 and Th2 cells have both been identified in airway biopsies of asthmatics but their role in mucus production is not clear. Using CD4 T cells from mice transgenic for the OVA-specific TCR, we studied the role of Th1 and Th2 cells in airway inflammation and mucus production. Airway inflammation induced by Th2 cells was comprised of eosinophils and lymphocytes; features found in asthmatic patients. Additionally, there was a marked increase in mucus production in mice that received Th2 cells and inhaled OVA, but not in mice that received Th1 cells. However, OVA-specific Th2 cells from IL-4–deficient mice were not recruited to the lung and did not induce mucus production. When this defect in homing was overcome by administration of TNF-α, IL-4 −/− Th2 cells induced mucus as effectively as IL-4 +/+ Th2 cells. These studies establish a role for Th2 cells in mucus production and dissect the effector functions of IL-4 in these processes. These data suggest that IL-4 is crucial for Th2 cell recruitment to the lung and for induction of inflammation, but has no direct role in mucus production.

scholarly journals MHC class II invariant chain–adjuvanted viral vectored vaccines enhances T cell responses in humans

2020 ◽  
Vol 12 (548) ◽  
pp. eaaz7715
Author(s):  
Ilaria Esposito ◽  
Paola Cicconi ◽  
Anna Morena D’Alise ◽  
Anthony Brown ◽  
Marialuisa Esposito ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Mhc Class Ii ◽  
T Cell Activation ◽  
Critical Role ◽  
T Cell Responses ◽  
Class Ii ◽  
Effector Memory ◽  
Invariant Chain ◽  
Cell Responses

Strategies to enhance the induction of high magnitude T cell responses through vaccination are urgently needed. Major histocompatibility complex (MHC) class II–associated invariant chain (Ii) plays a critical role in antigen presentation, forming MHC class II peptide complexes for the generation of CD4+ T cell responses. Preclinical studies evaluating the fusion of Ii to antigens encoded in vector delivery systems have shown that this strategy may enhance T cell immune responses to the encoded antigen. We now assess this strategy in humans, using chimpanzee adenovirus 3 and modified vaccinia Ankara vectors encoding human Ii fused to the nonstructural (NS) antigens of hepatitis C virus (HCV) in a heterologous prime/boost regimen. Vaccination was well tolerated and enhanced the peak magnitude, breadth, and proliferative capacity of anti-HCV T cell responses compared to non-Ii vaccines in humans. Very high frequencies of HCV-specific T cells were elicited in humans. Polyfunctional HCV-specific CD8+ and CD4+ responses were induced with up to 30% of CD3+CD8+ cells targeting single HCV epitopes; these were mostly effector memory cells with a high proportion expressing T cell activation and cytolytic markers. No volunteers developed anti-Ii T cell or antibody responses. Using a mouse model and in vitro experiments, we show that Ii fused to NS increases HCV immune responses through enhanced ubiquitination and proteasomal degradation. This strategy could be used to develop more potent HCV vaccines that may contribute to the HCV elimination targets and paves the way for developing class II Ii vaccines against cancer and other infections.

scholarly journals Identification of Two Distinct Subpopulations of Leishmania major-Specific T Helper 2 Cells

2002 ◽  
Vol 70 (10) ◽  
pp. 5512-5520 ◽  
Author(s):  
Pascale Kropf ◽  
Shanti Herath ◽  
Rita Tewari ◽  
Nelofer Syed ◽  
Roman Klemenz ◽  
...  
Keyword(s):  
T Cells ◽  
Leishmania Major ◽  
Lymphoid Organs ◽  
Cytokine Profile ◽  
Interleukin 4 ◽  
Th2 Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Th2 Response ◽  
T Helper 2

ABSTRACT It is widely accepted that a strong Th2 response is responsible for nonhealing Leishmania major infections in BALB/c mice. This Th2 response has been thoroughly documented by measuring the levels of Th2 cytokines produced by CD4+ T cells present in the lymphoid organs by enzyme-linked immunosorbent assay and PCR. However, the cytokine profile of L. major-specific Th2 cells has never been determined. In this study, we used the recently described Th2 marker T1/ST2 to characterize Th2 cells during the course of nonhealing L. major infection. We analyzed the intracellular cytokine profile of CD4+ T1/ST2+ T cells and showed that they clearly displayed a Th2 phenotype, as they expressed interleukin 4 (IL-4), IL-10, and IL-5. In addition, we detected another population of Th2 cells among the CD4+ T1/ST2− T cells that expressed IL-4 and IL-10 but excluded IL-5. In summary, we show here that two type 2 subpopulations are present in the lymphoid organs of L. major-infected BALB/c mice; Th2 cells from both subsets expressed IL-4 and IL-10, but they could be distinguished by their expression of IL-5 and T1/ST2.

Non-Plasmonic SERS with Silicon: Is It Really Safe? New Insights into Opto-Thermics of Core/Shell Microbeads

2018 ◽  
Author(s):  
Nicolò Bontempi ◽  
Irene Vassalini ◽  
Stefano Danesi ◽  
Matteo Ferroni ◽  
Paolo Colombi ◽  
...  
Keyword(s):  
Critical Role ◽  
Raman Laser ◽  
Core Shell ◽  
Thermal Coupling ◽  
Melting Points ◽  
Experimental Proof ◽  
Weakly Coupled ◽  
Light Management ◽  
Laser Sources ◽  
First Time

<p>Here we investigate for the first time the opto-thermal behavior of SiO<sub>2</sub>/Si core/shell microbeads (Si-rex) irradiated with three common Raman laser sources (lambda=532, 633, 785 nm) under real working conditions. We obtained an experimental proof of the critical role played by bead size and aggregation in heat and light management, demonstrating that in the case of strong opto-thermal coupling the temperature can exceed that of the melting points of both core and shell components. In addition, we also show that weakly coupled beads can be utilized as stable substrates for plasmon-free SERS experiments.</p>

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