scholarly journals Chronic Occupational Mold Exposure Drives Expansion of Aspergillus-Reactive Type 1 and Type 2 T-Helper Cell Responses

2021 ◽  
Vol 7 (9) ◽  
pp. 698
Author(s):  
Chris D. Lauruschkat ◽  
Sonja Etter ◽  
Elisabeth Schnack ◽  
Frank Ebel ◽  
Sascha Schäuble ◽  
...  
Keyword(s):  
Immune Cell ◽  
Allergic Diseases ◽  
T Helper ◽  
Cell Repertoire ◽  
Cell Responses ◽  
Th Cell ◽  
Organic Farmers ◽  
Occupationally Exposed ◽  
Mold Exposure ◽  
Th1 And Th2

Occupational mold exposure can lead to Aspergillus-associated allergic diseases including asthma and hypersensitivity pneumonitis. Elevated IL-17 levels or disbalanced T-helper (Th) cell expansion were previously linked to Aspergillus-associated allergic diseases, whereas alterations to the Th cell repertoire in healthy occupationally exposed subjects are scarcely studied. Therefore, we employed functional immunoassays to compare Th cell responses to A. fumigatus antigens in organic farmers, a cohort frequently exposed to environmental molds, and non-occupationally exposed controls. Organic farmers harbored significantly higher A. fumigatus-specific Th-cell frequencies than controls, with comparable expansion of Th1- and Th2-cell frequencies but only slightly elevated Th17-cell frequencies. Accordingly, Aspergillus antigen-induced Th1 and Th2 cytokine levels were strongly elevated, whereas induction of IL-17A was minimal. Additionally, increased levels of some innate immune cell-derived cytokines were found in samples from organic farmers. Antigen-induced cytokine release combined with Aspergillus-specific Th-cell frequencies resulted in high classification accuracy between organic farmers and controls. Aspf22, CatB, and CipC elicited the strongest differences in Th1 and Th2 responses between the two cohorts, suggesting these antigens as potential candidates for future bio-effect monitoring approaches. Overall, we found that occupationally exposed agricultural workers display a largely balanced co-expansion of Th1 and Th2 immunity with only minor changes in Th17 responses.

scholarly journals Lymphokine-mediated regulation of the proliferative response of clones of T helper 1 and T helper 2 cells.

1988 ◽  
Vol 168 (2) ◽  
pp. 543-558 ◽  
Author(s):  
R Fernandez-Botran ◽  
V M Sanders ◽  
T R Mosmann ◽  
E S Vitetta
Keyword(s):  
Proliferative Response ◽  
Th2 Cells ◽  
Th1 Cells ◽  
T Helper ◽  
T Helper 1 ◽  
Ifn Gamma ◽  
T Helper 2 ◽  
Regulatory Interactions ◽  
Th Cell ◽  
Th1 And Th2

Murine Th1 and Th2 subsets differ not only in the lymphokines they produce, but also functionally. It is not clear what factors influence the preferential activation of one subset versus the other and what regulatory interactions exist between them. The purpose of this study was to examine the effect of lymphokines produced by clones of Th1 cells (IL-2 and IFN-gamma), Th2 cells (IL-4), and APC (IL-1) on the proliferative response of Th1 and Th2 cells after antigenic stimulation. Activation of both types of clones in the presence of antigen and APC resulted in the acquisition of responsiveness to the proliferative effects of both IL-2 and IL-4, although Th2 cells were more responsive to IL-4 than Th1 cells. Responsiveness of Th1 and Th2 cells to both lymphokines decreased with time after initial antigenic activation; Th1 cells lost their responsiveness to IL-4 more rapidly and to IL-2 more slowly than Th2 cells. IFN-gamma partially inhibited the IL-2 and IL-4-mediated proliferation of Th2, but not Th1 cells. Although the presence of IL-1 was not required for the response of Th1 or Th2 cells to IL-4, its presence resulted in a synergistic effect with IL-2 or IL-4 in Th2 but not in Th1 cells. Both subsets responded to a mixture of IL-2 and IL-4 in synergistic fashion. Delayed addition and wash-out experiments indicated that both IL-2 and IL-4 had to be present simultaneously in order for synergy to occur. These results suggest that Th cell subsets might regulate each other via the lymphokines that they secrete and that the pathways of IL-2 and IL-4 mediated proliferation are interrelated.

scholarly journals Delayed maturation of an IL-12–producing dendritic cell subset explains the early Th2 bias in neonatal immunity

2008 ◽  
Vol 205 (10) ◽  
pp. 2269-2280 ◽  
Author(s):  
Hyun-Hee Lee ◽  
Christine M. Hoeman ◽  
John C. Hardaway ◽  
F. Betul Guloglu ◽  
Jason S. Ellis ◽  
...  
Keyword(s):  
Cell Subset ◽  
Th1 Cells ◽  
Dendritic Cell Subset ◽  
T Helper ◽  
Cell Responses ◽  
Th Cell ◽  
Neonatal Immunity ◽  
Low Levels ◽  
Delayed Maturation ◽  
Developmental Maturation

Primary neonatal T cell responses comprise both T helper (Th) cell subsets, but Th1 cells express high levels of interleukin 13 receptor α1 (IL-13Rα1), which heterodimerizes with IL-4Rα. During secondary antigen challenge, Th2-produced IL-4 triggers the apoptosis of Th1 cells via IL-4Rα/IL-13Rα1, thus explaining the Th2 bias in neonates. We show that neonates acquire the ability to overcome the Th2 bias and generate Th1 responses starting 6 d after birth. This transition was caused by the developmental maturation of CD8α+CD4− dendritic cells (DCs), which were minimal in number during the first few days of birth and produced low levels of IL-12. This lack of IL-12 sustained the expression of IL-13Rα1 on Th1 cells. By day 6 after birth, however, a significant number of CD8α+CD4− DCs accumulated in the spleen and produced IL-12, which triggered the down-regulation of IL-13Rα1 expression on Th1 cells, thus protecting them against IL-4–driven apoptosis.

scholarly journals CTLA-4 Engagement Inhibits Th2 but not Th1 Cell Polarisation

2003 ◽  
Vol 10 (1) ◽  
pp. 13-17 ◽  
Author(s):  
Vanessa Ubaldi ◽  
Lucia Gatta ◽  
Luigia Pace ◽  
Gino Doria ◽  
Claudio Pioli
Keyword(s):  
Transcriptional Activation ◽  
Cell Subset ◽  
Th2 Cells ◽  
T Helper ◽  
Th1 Cell ◽  
Th Cell ◽  
Ifn Γ ◽  
Culture Supernatants ◽  
Th1 And Th2

CTLA-4 deficient mice show severe lymphoproliferative disorders with T helper sub-population skewed toward the Th2 phenotype. In the present work, we investigated the role of CTLA-4 in T helper cell subset differentiation. Naïve CD4+cells were stimulated with anti-CD3 and anti-CD28 mAbs in the presence of either IL-12 or IL-4 to induce polarisation to Th1 or Th2 cells, respectively. Under these two polarising conditions cells express comparable levels of CTLA-4. CTLA-4 was stimulated by plastic-bound mAb. The frequency of IFN-γ- and IL-4-producing cells were estimated by FACS analysis. In parallel cultures, polarised Th1 and Th2 cells were re-stimulated with anti-CD3 and anti-CD28 mAbs for 48 h and their culture supernatants analysed by ELISA. Results show that CTLA-4 engagement during differentiation inhibits polarisation of naïve CD4+cells to the Th2 but not the Th1 cell subset. At variance, once cells are polarised, CTLA-4 engagement inhibits cytokine production in both effector Th2 and Th1 cells. Altogether these data indicate that CTLA-4 may interfere not only in the signalling involved in acute transcriptional activation of both Th1 and Th2 cells but also in the development of one of the Th cell subsets.

scholarly journals Human papillomavirus type 16 E2-specific T-helper lymphocyte responses in patients with cervical intraepithelial neoplasia

1999 ◽  
Vol 80 (9) ◽  
pp. 2453-2459 ◽  
Author(s):  
Hetty J. Bontkes ◽  
Tanja D. de Gruijl ◽  
Astrid Bijl ◽  
René H. M. Verheijen ◽  
Chris J. L. M. Meijer ◽  
...  
Keyword(s):  
Interleukin 2 ◽  
Human Papillomaviruses ◽  
T Helper ◽  
Cervical Lesions ◽  
Cytological Evidence ◽  
Hpv 16 ◽  
E2 Protein ◽  
Cell Responses ◽  
Terminal Domain ◽  
Th Cell

T-cell-mediated immune responses against mucosal oncogenic types of human papillomaviruses (HPV) are thought to play a role in the control of the virus infection and its associated cervical lesions. The in vitro production of interleukin-2 by T-helper (Th) cells in response to the C-terminal and N-terminal domains of the HPV-16 E2 protein was determined in 74 women with cytological evidence of premalignant cervical epithelial neoplasia who participated in a non-intervention follow-up (FU) study. Cross-sectional analysis at the end of FU showed that Th cell responses against the C-terminal domain were associated with evidence of previous or present HPV-16 infection as compared to patients with no evidence of any HPV infection (18·9% versus 0%, P=0·039). Th cell responses against the N-terminal domain were not associated with evidence of HPV-16 infection. No association with disease outcome was observed with Th cell responses against either of the E2 protein domains. However, longitudinal analysis revealed that Th cell responses against the C-terminal domain frequently occur at the time of virus clearance. Whether these responses are responsible for the clearance of the virus is not known.

scholarly journals TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand

2005 ◽  
Vol 202 (9) ◽  
pp. 1213-1223 ◽  
Author(s):  
Tomoki Ito ◽  
Yui-Hsi Wang ◽  
Omar Duramad ◽  
Toshiyuki Hori ◽  
Guy J. Delespesse ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Th2 Cells ◽  
T Helper ◽  
Cell Responses ◽  
Th Cell ◽  
Tnf Α ◽  
Ox40 Ligand ◽  
Helper Type

We recently showed that dendritic cells (DCs) activated by thymic stromal lymphopoietin (TSLP) prime naive CD4+ T cells to differentiate into T helper type 2 (Th2) cells that produced high amounts of tumor necrosis factor-α (TNF-α), but no interleukin (IL)-10. Here we report that TSLP induced human DCs to express OX40 ligand (OX40L) but not IL-12. TSLP-induced OX40L on DCs was required for triggering naive CD4+ T cells to produce IL-4, -5, and -13. We further revealed the following three novel functional properties of OX40L: (a) OX40L selectively promoted TNF-α, but inhibited IL-10 production in developing Th2 cells; (b) OX40L lost the ability to polarize Th2 cells in the presence of IL-12; and (c) OX40L exacerbated IL-12–induced Th1 cell inflammation by promoting TNF-α, while inhibiting IL-10. We conclude that OX40L on TSLP-activated DCs triggers Th2 cell polarization in the absence of IL-12, and propose that OX40L can switch IL-10–producing regulatory Th cell responses into TNF-α–producing inflammatory Th cell responses.

scholarly journals Dermal IRF4+ dendritic cells and monocytes license CD4+ T helper cells to distinct cytokine profiles

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Kerry L. Hilligan ◽  
Shiau-Choot Tang ◽  
Evelyn J. Hyde ◽  
Elsa Roussel ◽  
Johannes U. Mayer ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Lymph Node ◽  
T Helper Cells ◽  
Fungal Pathogens ◽  
T Helper ◽  
Cell Responses ◽  
Cytokine Responses ◽  
Th Cell ◽  
Th Differentiation

Abstract Antigen (Ag)-presenting cells (APC) instruct CD4+ helper T (Th) cell responses, but it is unclear whether different APC subsets contribute uniquely in determining Th differentiation in pathogen-specific settings. Here, we use skin-relevant, fluorescently-labeled bacterial, helminth or fungal pathogens to track and characterize the APC populations that drive Th responses in vivo. All pathogens are taken up by a population of IRF4+ dermal migratory dendritic cells (migDC2) that similarly upregulate surface co-stimulatory molecules but express pathogen-specific cytokine and chemokine transcripts. Depletion of migDC2 reduces the amount of Ag in lymph node and the development of IFNγ, IL-4 and IL-17A responses without gain of other cytokine responses. Ag+ monocytes are an essential source of IL-12 for both innate and adaptive IFNγ production, and inhibit follicular Th cell development. Our results thus suggest that Th cell differentiation does not require specialized APC subsets, but is driven by inducible and pathogen-specific transcriptional programs in Ag+ migDC2 and monocytes.

scholarly journals The Role of T Helper (TH)17 Cells as a Double-Edged Sword in the Interplay of Infection and Autoimmunity with a Focus on Xenobiotic-Induced Immunomodulation

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Nasr Y. A. Hemdan ◽  
Ahmed M. Abu El-Saad ◽  
Ulrich Sack
Keyword(s):  
Immune Cell ◽  
Critical Role ◽  
Cell Subset ◽  
Epidemiologic Studies ◽  
Experimental Models ◽  
Cell Responses ◽  
Th 17 ◽  
Xenobiotic Exposure ◽  
Occupationally Exposed

Extensive research in recent years suggests that exposure to xenobiotic stimuli plays a critical role in autoimmunity induction and severity and that the resulting response would be exacerbated in individuals with an infection-aroused immune system. In this context, heavy metals constitute a prominent category of xenobiotic substances, known to alter divergent immune cell responses in accidentally and occupationally exposed individuals, thereby increasing the susceptibility to autoimmunity and cancer, especially when accompanied by inflammation-triggered persistent sensitization. This perception is learned from experimental models of infection and epidemiologic studies and clearly underscores the interplay of exposure to such immunomodulatory elements with pre- or postexposure infectious events. Further, theTH17 cell subset, known to be associated with a growing list of autoimmune manifestations, may be the “superstar” at the interface of xenobiotic exposure and autoimmunity. In this review, the most recently established links to this nomination are short-listed to create a framework to better understand new insights intoTH17’s contributions to autoimmunity.

PRELI is a mitochondrial regulator of human primary T-helper cell apoptosis, STAT6, and Th2-cell differentiation

Blood ◽  
2009 ◽  
Vol 113 (6) ◽  
pp. 1268-1277 ◽  
Author(s):  
Johanna Tahvanainen ◽  
Teemu Kallonen ◽  
Hanna Lähteenmäki ◽  
Kaisa M. Heiskanen ◽  
Jukka Westermarck ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Differentiation ◽  
Allergic Diseases ◽  
Cell Receptor ◽  
T Helper ◽  
Th Cells ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway ◽  
Th2 Cell ◽  
Th Cell

Abstract The identification of novel factors regulating human T helper (Th)–cell differentiation into functionally distinct Th1 and Th2 subsets is important for understanding the mechanisms behind human autoimmune and allergic diseases. We have identified a protein of relevant evolutionary and lymphoid interest (PRELI), a novel protein that induces oxidative stress and a mitochondrial apoptosis pathway in human primary Th cells. We also demonstrated that PRELI inhibits Th2-cell development and down-regulates signal transducer and activator of transcription 6 (STAT6), a key transcription factor driving Th2 differentiation. Our data suggest that calpain, an oxidative stress–induced cysteine protease, is involved in the PRELI-induced down-regulation of STAT6. Moreover, we observed that a strong T-cell receptor (TCR) stimulus induces expression of PRELI and inhibits Th2 development. Our results suggest that PRELI is involved in a mechanism wherein the strength of the TCR stimulus influences the polarization of Th cells. This study identifies PRELI as a novel factor influencing the human primary Th-cell death and differentiation.

Augmentation of LTC4synthesis in human eosinophils caused by CD3-stimulated Th2-like cells in vitro

2000 ◽  
Vol 278 (6) ◽  
pp. L1172-L1179 ◽  
Author(s):  
Nilda M. Muñoz ◽  
Gijs A. van Seventer ◽  
Roshanak T. Semnani ◽  
Alan R. Leff
Keyword(s):  
Cytochalasin B ◽  
Th2 Cells ◽  
T Helper ◽  
Gm Csf ◽  
Th Cell ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Th1 And Th2

We assessed the effect of anti-CD3-stimulated secretion of cultured human Th1- and Th2-like cells on leukotriene C4(LTC4) secretion in isolated human eosinophils. T helper (Th) cell subsets were generated from human naive CD4+T cells cocultured with irradiated human transformed B cells and either recombinant human interleukin (rhIL)-1β plus rhIL-6 plus rhIL-12 for Th1-like cells or rhIL-1β plus rhIL-6 plus rhIL-4 for Th2-like cells. Coincubation of eosinophils with 1:5 dilution of Th2-supernatant (Sup) caused an increase in LTC4secretion caused by 0.1 μM formyl-Met-Leu-Phe and 5 μg/ml cytochalasin B from 921 ± 238 to 3,067 ± 1,462 pg/106eosinophils ( P < 0.01). Th1-Sup at the same dilution had no augmenting effect on stimulated secretion of LTC4in eosinophils despite substantial concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the supernatant. Dilution of Th1-Sup caused increased LTC4that returned to baseline after immunoabsorption of GM-CSF, suggesting the presence of a possible inhibitory factor. We demonstrate that pretreatment of eosinophils with 1:5 dilution of Th2-Sup but not of Th1-Sup causes substantial augmentation of LTC4secretion in vitro and establishes that human Th2 cells cause direct augmentation of LTC4secretion within 15–30 min of exposure.

scholarly journals Immunomodulatory Effects of Taiwanese Neolitsea Species on Th1 and Th2 Functionality

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Yin-Hua Cheng ◽  
Ying-Chi Lin ◽  
Ih-Sheng Chen ◽  
Sian-De Liu ◽  
Jih-Heng Li ◽  
...  
Keyword(s):  
T Helper Cells ◽  
Species Differences ◽  
T Helper ◽  
Cd4 Cells ◽  
Immunomodulatory Effects ◽  
Leaf Extracts ◽  
Th Cell ◽  
Th1 And Th2 Cytokines ◽  
Cell Functionality ◽  
Th1 And Th2

Neolitsea species, medicinal plants belonging to Lauraceae, contain rich alkaloids, steroids, sesquiterpenoids, and triterpenoids which possess antimicrobial, antioxidant, and anti-inflammatory bioactivities. However, species differences in the immunomodulatory effects and evidence pertaining to the effects of Neolitsea species on adaptive immunity are scarce. This study aimed to evaluate the immunomodulatory properties of ten Taiwanese Neolitsea plants on T helper (Th) cell functionality, especially Th1 and Th2. Most of the 29 crude extracts of Neolitsea were not toxic to splenocytes, except N. buisanensis roots. N. aciculata and N. villosa leaf extracts possessed differential immunomodulatory effects on Th1/Th2 balance. N. aciculata var. variabillima and N. hiiranensis leaf extracts attenuated both Th1 and Th2 cytokines while N. konishii dramatically suppressed IFN-γ production. As N. aciculata var. variabillima and N. konishii leaf extracts significantly attenuated Th1 functionality, we further evaluated their effects on CD4 cells under CD3/CD28 stimulation. N. aciculata var. variabillima significantly suppressed IFN-γ, IL-10, and IL-17, demonstrating the broad suppressive effects on T helper cells; N. konishii significantly suppressed IFN-γ and IL-10 production, while the production of IL-17 was not altered. Collectively, these data demonstrated that leaf extracts of Taiwanese Neolitsea species contain phytochemicals with potentials to be developed as selective immunomodulators.

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