scholarly journals Modulation of T helper 1 and T helper 2 immune balance in a stress mouse model during Chlamydia muridarum genital infection

2019 ◽  
Author(s):  
Tesfaye Belay ◽  
Elisha Martin ◽  
Gezelle Brown ◽  
Raenel Crenshaw ◽  
Julia Street ◽  
...  
Keyword(s):  
Mouse Model ◽  
Genital Infection ◽  
Th2 Cytokines ◽  
T Helper ◽  
T Helper 1 ◽  
Chlamydia Muridarum ◽  
T Helper 2 ◽  
Induced Stress ◽  
Ifn Γ ◽  
Th1 And Th2

ABSTRACTA mouse model to study the effect of cold-induced stress on Chlamydia muridarum genital infection and immune response has been developed in our laboratory. Our previous results show that cold-induced stress increases the intensity of chlamydia genital infection, but little is known about the effect of cold-induced stress on differentiations and activities of T cell subpopulations and bone marrow derived dendritic cells (BMDCs). The factors that regulate the production of T helper 1 (Th1) or T helper 2 (Th2) cytokines is not clear. The objective of this study was to examine whether cold-induced stress modulates the expression of transcription factors and hallmark cytokines of Th1 and Th2 or differentiation of BMDCs during C. muridarum genital infection in mice. Our results show that mRNA level of beta2-adrenergic receptor (β2-AR) compared to β1-AR and β3-AR was high in mixed population of CD4+ T cells and BMDCs. Further, decreased expression of T-bet and low level of interferon-gamma (IFN-γ) production and increased expression of GATA-3 and interleukin-4 (IL-4) production in CD4+ T of stressed mice was observed. Exposure of BMDCs to feroterol (β2-AR agonist) or ICI,118551 (β2-AR antagonist), respectively, revealed significant stimulation or inhibition of β2-AR in stressed mice. Moreover, co-culturing of mature BMDC and naïve CD4+ T cells resulted in increased production of IL-4, IL-10, and IL-17 in culture supernatants, suggesting that stimulation of β2-AR leads to the increased production of Th2 cytokines. Overall, our results show for the first time that cold-induced stress is able to modulate the pattern of Th1 and Th2 cytokine environment, suggesting that it promotes the differentiation to Th2 rather than Th1 by the overexpression of GATA-3 correlated with elevated production of IL-4, IL-10, IL-23, and IL-17 in contrast to a low expression of T-bet correlated with less IFN-γ secretion in the mouse model.

scholarly journals Modulation of T helper 1 and T helper 2 immune balance in a murine stress model during Chlamydia muridarum genital infection

PLoS ONE ◽  
2020 ◽  
Vol 15 (5) ◽  
pp. e0226539
Author(s):  
Tesfaye Belay ◽  
Elisha Martin ◽  
Gezelle Brown ◽  
Raenel Crenshaw ◽  
Julia Street ◽  
...  
Keyword(s):  
Genital Infection ◽  
Stress Model ◽  
T Helper ◽  
T Helper 1 ◽  
Chlamydia Muridarum ◽  
T Helper 2 ◽  
Immune Balance

Role of hormone-controlled T-cell cytokines in the maintenance of pregnancy

2000 ◽  
Vol 28 (2) ◽  
pp. 212-215 ◽  
Author(s):  
M.-P. Piccinni ◽  
E. Maggi ◽  
S. Romagnani
Keyword(s):  
T Cells ◽  
Embryo Implantation ◽  
Th2 Cells ◽  
Leukaemia Inhibitory Factor ◽  
Th2 Cytokines ◽  
T Helper ◽  
T Helper 1 ◽  
Apparent Paradox ◽  
Ifn Γ ◽  
Th1 And Th2

Human CD4 T helper lymphocytes can be subdivided into at least three distinct functional subsets on the basis of their cytokine secretion profiles. One type of CD4+ lymphocyte, T helper 1 (Th1), produces interferon (IFN)-γ and tumour necrosis factor β, a second type (Th2) produces interleukin (IL)-4 and IL-5 and a third type (Th0) produces both Th1 and Th2 cytokines. The apparent paradox that embryos are not rejected by the maternal immune system despite the presence of paternal MHC histocompatibility antigens has been explained in mice by a Th2 switch at the level of the materno-fetal interface. We showed that some hormones enhanced during pregnancy can affect the development of Th1 and Th2 responses. Indeed, we found that progesterone promotes the production of IL-4 and IL-5, whereas relaxin promotes the production of IFN-γ by T-cells. In addition, we showed that leukaemia inhibitory factor (LIF), which is essential for embryo implantation, associates with Th2 cells and is upregulated by IL-4 and progesterone. We also showed that LIF is down-regulated by Th1 inducers [IL-12, IFN-γ and IFN-α]. Further-more, we found a decreased production of LIF, IL-4 and IL-10 by decidual T-cells in women with unexplained recurrent abortions in comparison with women with normal gestation at the moment of voluntary abortion. The decreased production of LIF, IL-4 and IL-10 was not found in peripheral-blood T-cells. These results suggest that the local production of LIF and/or Th2 cytokines may contribute to the maintenance of pregnancy.

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.

Divergent Effects of Interleukin-4 and Interferon-γ on Macrophage-Derived Chemokine Production: An Amplification Circuit of Polarized T Helper 2 Responses

Blood ◽  
1998 ◽  
Vol 92 (8) ◽  
pp. 2668-2671 ◽  
Author(s):  
Raffaella Bonecchi ◽  
Silvano Sozzani ◽  
Johnny T. Stine ◽  
Walter Luini ◽  
Giovanna D’Amico ◽  
...  
Keyword(s):  
Constitutive Expression ◽  
Interferon Γ ◽  
Interleukin 4 ◽  
Th2 Cells ◽  
Mrna Levels ◽  
T Helper ◽  
T Helper 1 ◽  
Chemokine Production ◽  
T Helper 2 ◽  
Ifn Γ

Macrophage-derived chemokine (MDC) is a CC chemokine that recognizes the CCR4 receptor and is selective for T helper 2 (Th2) versus T helper 1 (Th1) cells. The present study was designed to investigate the effect of the prototypic Th2/Th1 cytokines, interleukin-4 (IL-4) and interferon-γ (IFN-γ), on the production of MDC by human monocytes. IL-4 and IL-13 caused a time-dependent (plateau at 24 hours) and concentration-dependent (EC50 2 and 10 ng/mL, respectively) increase of MDC mRNA levels in monocytes. Increased expression of MDC mRNA was associated with protein release in the supernatant. MDC expression and production induced by IL-4 and IL-13 were inhibited by IFN-γ. IFN-γ also suppressed the constitutive expression of MDC in mature macrophages and dendritic cells. These results delineate an amplification loop of polarized Th2 responses based on differential regulation of MDC production by IL-4 and IL-13 versus IFN-γ and on the selectivity of this chemokine for polarized Th2 cells. © 1998 by The American Society of Hematology.

scholarly journals Pengaruh Vaksinasi BCG Terhadap Serum Interferon Gamma pada Kasus Asma Ekstrinsik Atopi Anak

Sari Pediatri ◽  
2016 ◽  
Vol 10 (3) ◽  
pp. 207
Author(s):  
Yolanda Olivia Palandeng ◽  
Diana Devi Takumansang Sondakh
Keyword(s):  
Interferon Gamma ◽  
Control Group ◽  
T Helper ◽  
T Helper 1 ◽  
Control Group Design ◽  
T Helper 2 ◽  
Group Design ◽  
Ifn Γ

Latar belakang. Prevalensi asma makin meningkat, diduga berkaitan dengan kejadian infeksi pada anak yang menurun sehingga menyebabkan pergeseran keseimbangan antara limfosit T helper 1 (Th1) dan T helper 2 (Th2) ke arah predominan Th2. Infeksi mikobakterium dan vaksinasi BCG dapat meningkatkan respon imun Th1 (interferon gamma (IFN-γ)) dan menekan Th2.Tujuan. Mengetahui pengaruh vaksinasi BCG terhadap kadar IFN-γ serum pasien asma ekstrinsik atopi anak setelah vaksinasi BCG satu kali.Metode. Penelitian kuasi-eksperimental pretest posttest control group design pada anak asma atopi. Pengacakan perlakuan dilakukan terhadap subjek ke dalam kelompok BCG dan plasebo. Sebelum dan 8 minggu sesudah perlakuan diukur kadar IFN-γ serum.Hasil. Kadar IFN-γ serum tidak meningkat sesudah vaksinasi BCG (median 1,580 dan 0,780 pg/ml, p= 0,326) dan plasebo (median 1,255 dan 0,670 pg/ml, p= 0,079). Selisih kadar IFN-γ serum kelompok BCG dan plasebo tidak berbeda bermakna (median 0,020 dan -0,420 pg/ml, p= 0,449).Kesimpulan. Kadar IFN-γ serum pasien asma ekstrinsik atopi anak tidak meningkat setelah vaksinasi BCG 1 kali.

scholarly journals APRIL-producing eosinophils are involved in gastric MALT lymphomagenesis induced by Helicobacter sp infection

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Alice Blosse ◽  
Sara Peru ◽  
Michael Levy ◽  
Benoit Marteyn ◽  
Pauline Floch ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Mouse Model ◽  
Transgenic Mouse Model ◽  
Model Systems ◽  
Gastric Malt Lymphoma ◽  
T Helper ◽  
T Helper 1 ◽  
T Helper 2 ◽  
Tumorigenic Potential ◽  
Lymphoid Infiltrates

Abstract The roles of the inflammatory response and production of a proliferation-inducing ligand (APRIL) cytokine in gastric mucosa-associated lymphoid tissue (MALT) lymphomagenesis induced by Helicobacter species infection are not clearly understood. We characterized the gastric mucosal inflammatory response associated with gastric MALT lymphoma (GML) and identified APRIL-producing cells in two model systems: an APRIL transgenic mouse model of GML induced by Helicobacter infection (Tg-hAPRIL) and human gastric biopsy samples from Helicobacter pylori-infected GML patients. In the mouse model, polarization of T helper 1 (tbet), T helper 2 (gata3), and regulatory T cell (foxp3) responses was evaluated by quantitative PCR. In humans, a significant increase in april gene expression was observed in GML compared to gastritis. APRIL-producing cells were eosinophilic polynuclear cells located within lymphoid infiltrates, and tumoral B lymphocytes were targeted by APRIL. Together, the results of this study demonstrate that the Treg-balanced inflammatory environment is important for gastric lymphomagenesis induced by Helicobacter species, and suggest the pro-tumorigenic potential of APRIL-producing eosinophils.

scholarly journals Tacrolimus Improves the Implantation Rate in Patients with Elevated Th1/2 Helper Cell Ratio and Repeated Implantation Failure (RIF)

2020 ◽  
Vol 80 (08) ◽  
pp. 851-862
Author(s):  
Zahra Bahrami-Asl ◽  
Laya Farzadi ◽  
Amir Fattahi ◽  
Mehdi Yousefi ◽  
Alicia Quinonero ◽  
...  
Keyword(s):  
Implantation Rate ◽  
Live Birth Rate ◽  
Immunosuppressive Drug ◽  
Implantation Failure ◽  
T Helper ◽  
T Helper 1 ◽  
Repeated Implantation Failure ◽  
T Helper 2 ◽  
Tacrolimus Therapy ◽  
Ifn Γ

Abstract Introduction An abnormal endometrial immune response is involved in the pathogenesis of repeated implantation failure (RIF), so we investigated the effectiveness of tacrolimus treatment on the endometrium of RIF patients. Materials and Methods Ten RIF patients with elevated T-helper 1/T-helper 2 (Th1/Th2) cell ratios were recruited into a clinical study. The expression of p53, leukemia inhibitory factor (LIF), interleukin (IL)-4, IL-10, IL-17, and interferon gamma (IFN-γ) in the endometrium of patients with and without tacrolimus treatment and the association of these factors with assisted reproductive technology (ART) outcomes were investigated. Results Tacrolimus significantly increased the expression of LIF, IL-10, and IL-17 and decreased the expression of IL-4, IFN-γ, and the IFN-γ/IL-10 ratio in RIF patients. Tacrolimus treatment resulted in an implantation rate of 40%, a clinical pregnancy rate of 50%, and a live birth rate of 35% in RIF patients with elevated Th1/Th2 ratios who had previously failed to become pregnant despite at least three transfers of embryos. We also found a significant positive correlation between IL-10 levels and the implantation rate. Conclusions Our findings suggest that RIF patients with a higher Th1/Th2 ratio could be candidates for tacrolimus therapy and that this immunosuppressive drug could be acting through upregulation of LIF, IL-10, and IL-17.

Divergent Effects of Interleukin-4 and Interferon-γ on Macrophage-Derived Chemokine Production: An Amplification Circuit of Polarized T Helper 2 Responses

Blood ◽  
1998 ◽  
Vol 92 (8) ◽  
pp. 2668-2671 ◽  
Author(s):  
Raffaella Bonecchi ◽  
Silvano Sozzani ◽  
Johnny T. Stine ◽  
Walter Luini ◽  
Giovanna D’Amico ◽  
...  
Keyword(s):  
Constitutive Expression ◽  
Interferon Γ ◽  
Interleukin 4 ◽  
Th2 Cells ◽  
Mrna Levels ◽  
T Helper ◽  
T Helper 1 ◽  
Chemokine Production ◽  
T Helper 2 ◽  
Ifn Γ

Abstract Macrophage-derived chemokine (MDC) is a CC chemokine that recognizes the CCR4 receptor and is selective for T helper 2 (Th2) versus T helper 1 (Th1) cells. The present study was designed to investigate the effect of the prototypic Th2/Th1 cytokines, interleukin-4 (IL-4) and interferon-γ (IFN-γ), on the production of MDC by human monocytes. IL-4 and IL-13 caused a time-dependent (plateau at 24 hours) and concentration-dependent (EC50 2 and 10 ng/mL, respectively) increase of MDC mRNA levels in monocytes. Increased expression of MDC mRNA was associated with protein release in the supernatant. MDC expression and production induced by IL-4 and IL-13 were inhibited by IFN-γ. IFN-γ also suppressed the constitutive expression of MDC in mature macrophages and dendritic cells. These results delineate an amplification loop of polarized Th2 responses based on differential regulation of MDC production by IL-4 and IL-13 versus IFN-γ and on the selectivity of this chemokine for polarized Th2 cells. © 1998 by The American Society of Hematology.

scholarly journals OX40L–OX40 Signaling in Atopic Dermatitis

2021 ◽  
Vol 10 (12) ◽  
pp. 2578
Author(s):  
Masutaka Furue ◽  
Mihoko Furue
Keyword(s):  
T Cells ◽  
Atopic Dermatitis ◽  
Memory T Cells ◽  
Effector Memory ◽  
T Helper ◽  
T Helper 1 ◽  
Therapeutic Success ◽  
T Helper 2 ◽  
Promising Target ◽  
Antigen Presenting

OX40 is one of the co-stimulatory molecules expressed on T cells, and it is engaged by OX40L, primarily expressed on professional antigen-presenting cells such as dendritic cells. The OX40L–OX40 axis is involved in the sustained activation and expansion of effector T and effector memory T cells, but it is not active in naïve and resting memory T cells. Ligation of OX40 by OX40L accelerates both T helper 1 (Th1) and T helper 2 (Th2) effector cell differentiation. Recent therapeutic success in clinical trials highlights the importance of the OX40L–OX40 axis as a promising target for the treatment of atopic dermatitis.

Remission of Alopecia Universalis after 1 Year of Treatment with Dupilumab in a Patient with Severe Atopic Dermatitis

2021 ◽  
pp. 1-4
Author(s):  
Maurizio Romagnuolo ◽  
Mauro Barbareschi ◽  
Simona Tavecchio ◽  
Luisa Angileri ◽  
Silvia Mariel Ferrucci
Keyword(s):  
Atopic Dermatitis ◽  
Skin Disorder ◽  
Human Monoclonal Antibody ◽  
Severe Atopic Dermatitis ◽  
T Helper ◽  
T Helper 1 ◽  
Th2 Response ◽  
Alopecia Universalis ◽  
T Helper 2 ◽  
Relapsing Remitting

Alopecia areata (AA), an autoimmune disease with a relapsing-remitting course, represents the second cause of non­scarring alopecia worldwide and is associated with several comorbidities, notably atopic dermatitis (AD). In particular, AD is related to its more severe forms alopecia totalis (AT) and alopecia universalis (AU) [Nat Rev Dis Primers. 2017;3:17011]. Considering that AA has been classified as T helper 1-driven disease, whereas AD is the prototypical T helper 2 (Th2)-driven skin disorder, recent studies suggest that these forms may underlie a different chemokine expression resulting in a Th2 skewing as a key pathomechanism that could explain this association [JAMA Dermatol. 2015 May;151(5):522–8]. Several reports showed that dupilumab, a fully human monoclonal antibody targeting the interleukin 4α receptor and thus downregulating Th2 response, led to an improvement of AA associated with AD; most of these patients were females with AT or AU, early-onset AD, and atopic comorbidities [Exp Dermatol. 2020 Aug;29(8):726–32]. We report here a case to further support this hypothesis.

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