scholarly journals Ontogeny of Th1 Memory Responses against a Brucella abortus Conjugate

2001 ◽  
Vol 69 (9) ◽  
pp. 5417-5422 ◽  
Author(s):  
Orit Scharf ◽  
Inna Agranovich ◽  
Katherine Lee ◽  
Nancy L. Eller ◽  
Lily Levy ◽  
...  
Keyword(s):  
Brucella Abortus ◽  
Immunoglobulin E ◽  
Single Injection ◽  
Allergen Challenge ◽  
Th2 Cells ◽  
Interleukin 12 ◽  
Th2 Response ◽  
Immune Development ◽  
Ifn Γ ◽  
Old Mice

ABSTRACT Protective immune responses to intracellular pathogens such asBrucella abortus are characteristically Th1-like. Recently we demonstrated that heat-killed B. abortus (HKBa), a strong Th1 stimulus, conjugated to ovalbumin (HKBA-OVA), but notB. abortus alone, can alter the antigen-specific cytokine profile from Th2- to Th1-like. In this report we study the ability of a single injection of B. abortus to switch a Th2 to a Th1 response in immature mice. One-day- and 1-week-old mice were given a single injection of B. abortus in the absence or presence of OVA, and at maturity mice were challenged with an allergenic preparation, OVA with alum (OVA-A). B. abortus given without OVA did not diminish the subsequent Th2 response in either age group. In contrast, mice receiving a single injection of B. abortus-OVA at the age of 1 week, but not those injected at the age of 1 day, had reversal of the ratio of OVA-specific Th1 to Th2 cells and decreased immunoglobulin E levels after allergen challenge as adults. Within 6 h both 1-day- and 1-week-old mice expressed interleukin-12 p40 mRNA following either B. abortus orB. abortus-OVA administration. However, only the 1-week-old mice exhibited increased expression of gamma interferon (IFN-γ) mRNA. The absence of the early IFN-γ response in 1-day-old mice may explain their inability to generate a Th1 memory response. These results suggest that at early stages of immune development, responses to intracellular bacteria may be Th2- rather than Th1-like. Furthermore, they suggest that the first encounter with antigen evokes either a Th1- or a Th2-like response which becomes imprinted, so that subsequent memory responses conform to the original Th bias. This has implications for protection against infectious agents and development of allergic responses.

scholarly journals Down-Regulation of Th2 Responses by Brucella abortus, a Strong Th1 Stimulus, Correlates with Alterations in the B7.2-CD28 Pathway

1999 ◽  
Vol 67 (9) ◽  
pp. 4418-4426 ◽  
Author(s):  
Inna Agranovich ◽  
Dorothy E. Scott ◽  
Douglas Terle ◽  
Katherine Lee ◽  
Basil Golding
Keyword(s):  
T Cells ◽  
Brucella Abortus ◽  
Costimulatory Molecules ◽  
Th2 Cells ◽  
Interleukin 12 ◽  
Antibody Treatment ◽  
Th2 Response ◽  
Down Regulation ◽  
Th2 Responses ◽  
Ifn Γ

ABSTRACT Down-regulation of the Th2-like response induced by ovalbumin-alum (OVA/alum) immunization by heat-killed Brucella abortus was not reversed by anti-IL-12 antibody treatment or in gamma interferon (IFN-γ) knockout mice, suggesting that induction of Th1 cytokines was not the only mechanism involved in the B. abortus-mediated inhibition of the Th2 response to OVA/alum. The focus of this study was to determine whether an alternative pathway involves alteration in expression of costimulatory molecules. First we show that the Th2-like response to OVA/alum is dependent on B7.2 interaction with ligand since it can be abrogated by anti-B7.2 treatment. Expression of costimulatory molecules was then studied in mice immunized with OVA/alum in the absence or presence of B. abortus. B7.2, but not B7.1, was up-regulated on mouse non-T and T cells following immunization withB. abortus. Surprisingly, B. abortus induced down-regulation of CD28 and up-regulation of B7.2 on murine CD4+ and CD8+ T cells. These effects on T cells were maximal for CD28 and B7.2 at 40 to 48 h and were not dependent on interleukin-12 (IL-12) or IFN-γ. On the basis of these results, we propose that the IL-12/IFN-γ-independent inhibition of Th2 responses to OVA/alum is secondary to the effects of B. abortus on expression of costimulatory molecules on T cells. We suggest that down-regulation of CD28 following activation inhibits subsequent differentiation of Th0 into Th2 cells. In addition, decreased expression of CD28 and increased expression of B7.2 on T cells would favor B7.2 interaction with CTLA-4 on T cells, and this could provide a negative signal to developing Th2 cells.

scholarly journals Th2-driven, allergen-induced airway inflammation is reduced after treatment with anti–Tim-3 antibody in vivo

2007 ◽  
Vol 204 (6) ◽  
pp. 1289-1294 ◽  
Author(s):  
Jennifer Kearley ◽  
Sarah J. McMillan ◽  
Clare M. Lloyd
Keyword(s):  
Pulmonary Inflammation ◽  
Allergen Challenge ◽  
Airway Hyperreactivity ◽  
Th2 Cells ◽  
Antibody Treatment ◽  
Th2 Response ◽  
Th2 Cytokine ◽  
Cytokine Levels ◽  
Ifn Γ

T cell immunoglobulin and mucin domain–containing molecule-3 (Tim-3) is a surface molecule that is preferentially expressed on activated Th1 cells in comparison to Th2 cells. Blockade of Tim-3 has been shown to enhance Th1-driven pathology in vivo, suggesting that blockade of Tim-3 may improve the development of Th2-associated responses such as allergy. To examine the effects of Tim-3 blockade on the Th2 response in vivo, we administered anti–Tim-3 antibody during pulmonary inflammation induced by transfer of ovalbumin (OVA)-reactive Th2 cells, and subsequent aerosol challenge with OVA. In this model, anti–Tim-3 antibody treatment before each airway challenge significantly reduced airway hyperreactivity, with a concomitant decrease in eosinophils and Th2 cells in the lung. We examined Th1 and Th2 cytokine levels in the lung after allergen challenge and found that pulmonary expression of the Th2 cytokine IL-5 was significantly reduced, whereas IFN-γ levels were significantly increased by anti–Tim-3 antibody treatment. Thus, blocking Tim-3 function has a beneficial effect during pulmonary inflammation by skewing the Th2 response toward that of a Th1 type, suggesting an important role for Tim-3 in the regulation of allergic disease.

scholarly journals Immunostimulatory oligonucleotides block allergic airway inflammation by inhibiting Th2 cell activation and IgE-mediated cytokine induction

2005 ◽  
Vol 202 (11) ◽  
pp. 1563-1573 ◽  
Author(s):  
Edith M. Hessel ◽  
Mabel Chu ◽  
Jennifer O. Lizcano ◽  
Bonnie Chang ◽  
Nancy Herman ◽  
...  
Keyword(s):  
Cell Activation ◽  
Immunoglobulin E ◽  
Allergen Challenge ◽  
Allergic Airway Inflammation ◽  
Interleukin 4 ◽  
Th2 Cells ◽  
Functional Responses ◽  
Th2 Response ◽  
Airway Responses

A single treatment with a CpG-containing immunostimulatory DNA sequence (ISS) given before allergen challenge can inhibit T helper type 2 cell (Th2)–mediated airway responses in animal models of allergic asthma; however, the mechanism of this inhibition remains largely undefined. Here, we demonstrate that airway delivery of ISS before allergen challenge in Th2-primed mice acts in two distinct ways to prevent the allergic responses to this challenge. The first is to prevent induction of cytokines from allergen-specific Th2 cells, as demonstrated by the nearly complete inhibition of Th2 cytokine production, Th2-dependent functional responses, and gene induction patterns. ISS inhibits the Th2 response by rendering lung antigen-presenting cells (APCs) unable to effectively present antigen to Th2 cells, but not to Th1 cells. This loss of APC function correlates with a reduced expression of costimulatory molecules, including programmed cell death ligand (PD-L)1, PD-L2, CD40, CD80, CD86, and inducible T cell costimulator, and of major histocompatibility complex class II on CD11c+APCs from the airways of ISS-treated mice. The second important action of ISS is inhibition of immunoglobulin E–dependent release of Th2 cytokines, especially interleukin 4, from basophils and/or mast cells in the airways of Th2-primed mice. Thus, inhibition by ISS of allergic responses can be explained by two novel mechanisms that culminate in the inhibition of the principal sources of type 2 cytokines in the airways.

scholarly journals Protective effects of combined Mycobacterium bovis BCG and interleukin-12 vaccination on airway inflammation in a murine model of allergic asthma

2010 ◽  
Vol 33 (3) ◽  
pp. 196 ◽  
Author(s):  
Xia Ke ◽  
Jiangju Huang ◽  
Quan Chen ◽  
Suling Hong ◽  
Daoyin Zhu
Keyword(s):  
Airway Inflammation ◽  
Allergic Asthma ◽  
Mycobacterium Bovis ◽  
Immunoglobulin E ◽  
Allergic Airway Inflammation ◽  
Interleukin 12 ◽  
Protective Effects ◽  
Th2 Response ◽  
Bcg Vaccination ◽  
Th2 Responses

Purpose. Allergic asthma is characterized by chronic airway inflammation and airway hyperresponsiveness driven by allergen-specific T helper (Th)2 cells. Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccination has been documented to suppress Th2 responses and allergic airway inflammation in animal models. Since interleukin (IL)-12 is capable of inhibiting Th2 responses, we sought to investigate whether IL-12 could function as an adjuvant to increase the efficacy of BCG vaccination against allergic asthma. Methods. BALB/c neonatal mice (24 mice, 48-72 h old) were randomly divided into 3 subgroups (n = 8 for each group) to be immunized with PBS (control) or BCG with or without DNA plasmid-expressing IL-12. All of the mice were then sensitized and provoked with ovalbumin (OVA) to establish a model of allergic asthma. Results. Mice vaccinated with BCG alone showed a significant reduction in airway inflammation, percentage of eosinophils in bronchoalveolar lavage (BAL) fluid, and serum OVA-specific immunoglobulin E (IgE) levels in comparison with control animals. The suppressive effects of BCG were substantially augmented by the combination with IL-12. Furthermore, a decreased IL-4 and increased interferon-gamma (IFN-γ) production in BAL fluid were observed in animals inoculated with BCG alone or with IL-12 relative to control animals. Conclusion. Our data indicate that the combined vaccination with BCG and IL-12 yields a favorable outcome in prevention of experimental allergic airway inflammation, which is likely mediated through triggering a shift from a Th2 response to a Th1 response.

scholarly journals Requirements for in vivo IFN-γ induction by live microfilariae of the parasitic nematode, Brugia malayi

Parasitology ◽  
2000 ◽  
Vol 120 (6) ◽  
pp. 631-640 ◽  
Author(s):  
R. A. LAWRENCE ◽  
J. E. ALLEN ◽  
C. A. GRAY
Keyword(s):  
Human Disease ◽  
Parasitic Nematode ◽  
Prolonged Exposure ◽  
Brugia Malayi ◽  
Th2 Cells ◽  
Th2 Response ◽  
Antibody Isotypes ◽  
Ifn Γ ◽  
Higher Doses

Lymphatic filariasis caused by the parasitic nematode, Brugia malayi, is a chronic human disease immunologically characterized by stimulation of Th2 cells and reduced antigen-specific T cell responses. Single stage intra-peritoneal infections with infective larvae (L3) or adult nematodes induce Th2 cells, while the microfilarial stage (Mf) stimulates IFN-γ and Mf-specific IgG1, IgG2a, IgG2b, IgG3 and IgM, but not IgE. To investigate whether IFN-γ is elicited by live Mf in their natural site of infection, mice were infected intravenously. Intravenous infection had a striking effect on the response to Mf and high levels of IgE were induced even in the presence of IFN-γ. Indeed IgE levels to Mf increased markedly with the number of immunizations, higher doses of Mf and prolonged exposure to Mf suggesting that under conditions of chronic antigen exposure, typical of human disease, Mf will stimulate high levels of IgE. The ability of Mf-induced IFN-γ to modulate or regulate a pre-existing Th2 response, was investigated by infecting mice initially with adult male worms to induce a Th2 response, followed 14 days later by infection with Mf. Although Mf stimulated IFN-γ in the presence of male adults, the antibody isotypes elicited did not reflect IFN-γ induction and IgG1and IgE dominated the response. Although it cannot be discounted that IFN-γ induction by Mf may act locally as an inflammatory mediator or modulator of Th2 cells, these data suggest that Mf-stimulated IFN-γ does not have a profound effect overall on progression of the Th2-dominated immune response to filarial infection.

scholarly journals Apigenin Attenuates Allergic Responses of Ovalbumin-Induced Allergic Rhinitis Through Modulation of Th1/Th2 Responses in Experimental Mice

Dose-Response ◽  
2020 ◽  
Vol 18 (1) ◽  
pp. 155932582090479 ◽  
Author(s):  
Feng Chen ◽  
Dongyun He ◽  
Bailing Yan
Keyword(s):  
Allergic Rhinitis ◽  
Messenger Rna ◽  
Immunoglobulin E ◽  
Elevated Serum ◽  
Lavage Fluid ◽  
Specific Ige ◽  
Cytokine Signaling ◽  
Nuclear Factor ◽  
Th2 Response ◽  
Ifn Γ

Background: Allergic rhinitis (AR) is an immunoglobulin E (IgE)-mediated immune-inflammatory response mainly affecting nasal mucosa. Apigenin, a flavonoid, has been documented to possess promising anti-allergic potential. Aim: To determine the potential mechanism of action of apigenin against ovalbumin (OVA)-induced AR by assessing various behavioral, biochemical, molecular, and ultrastructural modifications. Materials and Methods: Allergic rhinitis was induced in BALB/c mice (18-22 grams) by sensitizing it with OVA (5%, 500 μL, intraperitoneal [IP] on each consecutive day, for 13 days) followed by intranasal challenge with OVA (5%, 5 μL per nostril on day 21). Animals were treated with either vehicle (distilled water, 10 mg/kg, IP) or apigenin (5, 10, and 20 mg/kg, IP). Results: Intranasal challenge of OVA resulted in significant induction ( P < .05) of AR reflected by an increase in nasal symptoms (sneezing, rubbing, and discharge), which were ameliorated significantly ( P < .05) by apigenin (10 and 20 mg/kg) treatment. It also significantly inhibited ( P < .05) OVA-induced elevated serum histamine, OVA-specific IgE, total IgE, and IgG1 and β-hexosaminidase levels. Ovalbumin-induced increased levels of interleukin (IL)-4, IL-5, IL-13, and interferon (IFN)-γ in nasal lavage fluid were significantly decreased ( P < .05) by apigenin. Ovalbumin-induced alterations in splenic GATA binding protein 3 (ie, erythroid transcription factor) (GATA3), T-box protein expressed in T cells (T-bet), signal transducer and activator of transcription-6 (STAT6), suppressor of cytokine signaling 1 (SOCS1), nuclear factor-kappa B (NF-κB), and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha messenger RNA, as well as protein expressions were significantly inhibited ( P < .05) by apigenin. It also significantly ameliorated ( P < .05) nasal and spleen histopathologic and ultrastructure aberration induced by OVA. Conclusion: Apigenin regulates Th1/Th2 balance via suppression in expressions of Th2 response (IgE, histamine, ILs, GATA3, STAT6, SOCS1, and NF-κB) and activation of Th1 response (IFN-γ and T-bet) to exert its anti-allergic potential in a murine model of OVA-induced AR.

Kinetic Th1/Th2 responses of transgenic mice with bacterial meningitis induced by Haemophilus influenzae

2006 ◽  
Vol 111 (4) ◽  
pp. 253-263 ◽  
Author(s):  
Shyi-Jou Chen ◽  
Mong-Ling Chu ◽  
Chia-Jen Wang ◽  
Ching-Len Liao ◽  
Shie-Liang Hsieh ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Haemophilus Influenzae ◽  
Clinical Symptoms ◽  
Specific Antigen ◽  
Clinical Severity ◽  
Interleukin 4 ◽  
Th2 Cells ◽  
Th1 Cells ◽  
Th2 Response ◽  
Ifn Γ

To investigate the kinetic Th1/Th2 immunopathogenic mechanisms of Haemophilus influenzae meningitis, we established a murine experimental model of meningitis and elucidated the Th1/Th2 immune responses in T1/T2 doubly transgenic mice based on a BALB/c background under the control of the IFN-γ (interferon-γ)/IL-4 (interleukin-4) promoters respectively. NTHi (non-typeable Haemophilus influenzae) meningitis was induced in these mice by inoculation with either a colonized (CNTHi) or invasive (INTHi) strain of NTHi. Mice inoculated with CNTHi displayed a less severe degree of disease in terms of clinical symptoms, mortality rate and brain histopathology. Conversely, INTHi-inoculated mice had more severe clinical symptoms. CNTHi-inoculated mice had a more significant Th1 response in terms of a higher percentage and longer maintenance of Th1 cells, and more production of IFN-γ from strain-specific antigen-stimulated splenocytes than INTHi-inoculated mice. In contrast, INTHi-inoculated mice had a more significant Th2 response. This was due to a significant increase in IL-4-producing CD4+ T-cells (Th2 cells) and more production of IL-4 from strain-specific antigen-stimulated splenocytes accompanied by a rapid decline of Th1 cells in INTHi-inoculated mice. In conclusion, the preferential Th1/Th2 trend in this murine model of NTHi meningitis is correlated with clinical severity as well as isolated characteristics of the pathogens themselves.

scholarly journals Adaptive Immune Responses Mediated Age-related Plasmodium yoelii 17XL and 17XNL Infections in 4 and 8-week-old BALB/c Mice

2020 ◽  
Author(s):  
Qiu-bo Wang ◽  
Yun-ting Du ◽  
Fei Liu ◽  
Xiao-dan Sun ◽  
Xun Sun ◽  
...  
Keyword(s):  
T Cells ◽  
Survival Rate ◽  
Plasmodium Yoelii ◽  
Th2 Cells ◽  
Dependent Manner ◽  
Adaptive Immune ◽  
Age Related ◽  
Specific Igg ◽  
Ifn Γ ◽  
Old Mice

Abstract Backgroud: As the quest to eradicate malaria continues, it is important to clarify the opposite clinical outcomes between children and adulthood. The relationship between adaptive immune response and age-related malaria infection remains unknown.Methods: 4 and 8-week-old mice were used to mimic children and adulthood, respectively. Parasitemia and the survival rate were monitored. The proportion and function of Th1 and Th2 cells were detected by FACS. The levels of IFN-γ, IL-4, total IgG, IgG1, IgG2a and Plasmodium yoelii MSP-1-specific IgG were measured by ELISA.Results: Our results found that childhood mice were more susceptible to P. yoelii 17XNL infection, with lower survival rate and higher parasitemia. The adult group showed greater resistance to P. yoelii 17XL infection, with lower parasitemia. Compared with 4-week-old mice, the percentage of CD4+T-bet+IFN-γ+ Th1 cells as well as IFN-γ production were significantly increased on day 5 p.i. in the 8-week-old mice after P. yoelii 17XNL infection. The percentage of CD4+GATA3+IL-4+ Th2 cells and CD4+CXCR5+ Tfh cells, and IL-4 production in the 8-week-old mice significantly increased on day 5 and day 10 after P. yoelii 17XNL infection. Notably, the levels of total IgG, IgG1, IgG2a and P. yoelii MSP-1-specific IgG were also significantly increased in the 8-week-old mice. PD-1, a marker of exhaustion, was up-regulated on CD4+ or activated CD4+ T cells in the 8-week-old mice as compared to the 4-week-old group.Conclusions: Thus, we consider that enhanced cellular and humoral adaptive immunity might contribute to rapid clearance of malaria among adults, likely in a PD-1-dependent manner due to induction of CD4+ T cells exhaustion in P. yoelii 17XNL infected 8-week-old mice.

scholarly journals Adaptive Immune Responses Mediated Age-related Plasmodium yoelii 17XL and 17XNL Infections in 4 and 8-week-old BALB/c Mice

2019 ◽  
Author(s):  
Qiu-bo Wang ◽  
Yun-ting Du ◽  
Fei Liu ◽  
Xiao-dan Sun ◽  
Xun Sun ◽  
...  
Keyword(s):  
T Cells ◽  
Survival Rate ◽  
Cd4 T Cells ◽  
Plasmodium Yoelii ◽  
Th2 Cells ◽  
Dependent Manner ◽  
Adaptive Immune ◽  
Age Related ◽  
Ifn Γ ◽  
Old Mice

Abstract Background As the quest to eradicate malaria continues, it is important to clarify the opposite clinical outcomes between childhood and adulthood. The relationship between adaptive immune response and age-related malaria infection remains unknown. Methods 4 and 8-week-old mice were used to mimic childhood and adulthood, respectively. Parasitemia and the survival rate were monitored. The proportion and function of Th1 and Th2 cells were detected by FACS. The levels of IFN-γ, IL-4, total IgG, IgG1, IgG2a and Plasmodium yoelii MSP-1-special IgG were measured by ELISA. Results Infant mice were more susceptible to P. yoelii 17XNL infection, with lower survival rate and higher parasitemia. The adult group showed greater resistance to P. yoelii 17XL infection, with lower parasitemia. Compared with 4-week-old mice, the percentage of CD4 + T-bet + IFN-γ + Th1 cells as well as IFN-γ production were significantly increased on day 5 p.i. in the 8-week-old mice after P. yoelii 17XNL infection. The percentage of CD4 + GATA3 + IL-4 + Th2 cells and CD4 + CXCR5 + Tfh cells, and IL-4 production in the 8-week-old mice obviously increased on day 5 and day 10 after P. yoelii 17XNL infection. Notably, the levels of total IgG, IgG1, IgG2a and P. yoelii MSP-1-special IgG were also significantly increased in the 8-week-old mice. PD-1, a marker of exhaustion, was up-regulated on CD4 + or activated CD4 + T cells in the 8-week-old mice as compared to the 4-week-old group. Conclusion We consider that enhanced cellular and humoral adaptive immunity might contribute to rapid clearance of malaria among adults, likely in a PD-1-dependent manner due to induction of CD4 + T cells exhaustion.

scholarly journals Adaptive Immune Responses Mediated Age-related Plasmodium yoelii 17XL and 17XNL Infections in 4 and 8-week-old BALB/c Mice

2020 ◽  
Author(s):  
Qiu-bo Wang ◽  
Yun-ting Du ◽  
Fei Liu ◽  
Xiao-dan Sun ◽  
Xun Sun ◽  
...  
Keyword(s):  
T Cells ◽  
Survival Rate ◽  
Plasmodium Yoelii ◽  
Th2 Cells ◽  
Dependent Manner ◽  
Adaptive Immune ◽  
Age Related ◽  
Specific Igg ◽  
Ifn Γ ◽  
Old Mice

Abstract Backgroud: As the quest to eradicate malaria continues, it is important to clarify the opposite clinical outcomes between childhood and adulthood. The relationship between adaptive immune response and age-related malaria infection remains unknown. Methods: 4 and 8-week-old mice were used to mimic childhood and adulthood, respectively. Parasitemia and the survival rate were monitored. The proportion and function of Th1 and Th2 cells were detected by FACS. The levels of IFN-γ, IL-4, total IgG, IgG1, IgG2a and Plasmodium yoelii MSP-1-specific IgG were measured by ELISA. Results: Our results found that childhood mice were more susceptible to P. yoelii 17XNL infection, with lower survival rate and higher parasitemia. The adult group showed greater resistance to P. yoelii 17XL infection, with lower parasitemia. Compared with 4-week-old mice, the percentage of CD4+T-bet+IFN-γ+ Th1 cells as well as IFN-γ production were significantly increased on day 5 p.i. in the 8-week-old mice after P. yoelii 17XNL infection. The percentage of CD4+GATA3+IL-4+ Th2 cells and CD4+CXCR5+ Tfh cells, and IL-4 production in the 8-week-old mice significantly increased on day 5 and day 10 after P. yoelii 17XNL infection. Notably, the levels of total IgG, IgG1, IgG2a and P. yoelii MSP-1-specific IgG were also significantly increased in the 8-week-old mice. PD-1, a marker of exhaustion, was up-regulated on CD4+ or activated CD4+ T cells in the 8-week-old mice as compared to the 4-week-old group. Conclusions: Thus, we consider that enhanced cellular and humoral adaptive immunity might contribute to rapid clearance of malaria among adults, likely in a PD-1-dependent manner due to induction of CD4+ T cells exhaustion in P. yoelii 17XNL infected 8-week-old mice.

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