scholarly journals Effects of Macrolide Antibiotics on Th1 Cell and Th2 Cell Development Mediated by Langerhans Cells

2016 ◽  
Vol 19 (3) ◽  
pp. 357 ◽  
Author(s):  
Katsuhiko Matsui ◽  
Saki Tamai ◽  
Reiko Ikeda
Keyword(s):  
Langerhans Cells ◽  
Cell Development ◽  
Th2 Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Macrolide Antibiotics ◽  
Mouse Bone Marrow ◽  
Down Regulation ◽  
Th1 Cell ◽  
Th2 Cell ◽  
Th2 Immune Response

ABSTRACT - Background: It is well known that Langerhans cells (LCs) work as the primary orchestrators in the polarization of the immune milieu towards a T helper type 1 (Th1) or a Th2 immune response. In this study, we investigated the effects of macrolide antibiotics on Th1 cell and Th2 cell development mediated by LCs. Methods: LC-like dendritic cells (LDCs) were generated from mouse bone marrow cells and used as substitutes for LCs. Mice were primed with ovalbumin (OVA) peptide-pulsed LDCs, which had been treated with each macrolide antibiotic, via the hind footpad. After 5 days, the cytokine response in the popliteal lymph nodes was investigated by enzyme-linked immunosorbent assay. The expression of cell surface molecules on LDCs was investigated using reverse transcriptase polymerase chain reaction. Results: Injection of OVA peptide-pulsed LDCs, which had been treated with josamycin or spiramycin, inhibited Th2 cell development as represented by down-regulation of interleukin (IL)-4 production as well as Th1 cell development as represented by down-regulation of interferon (IFN)-g production. This inhibition of Th1 cell and Th2 cell development was associated with suppression of CD86 and T-cell immunoglobulin and mucin domain-containing protein (TIM)-4 expression, respectively, in LDCs. Furthermore, Staphylococcus aureus strains isolated from skin lesions of patients with atopic dermatitis (AD) were more susceptible to josamycin than to spiramycin. Conclusions:  These results suggest that topical application of josamycin to AD lesions colonized with S. aureus would be beneficial for control of AD by acting on both superficial S. aureus and epidermal LCs, and inhibiting the development of Th2 cells.

scholarly journals Effects of anti-allergy drugs on Th1 cell and Th2 cell development mediated by Langerhans cells

2020 ◽  
Vol 23 ◽  
pp. 412-421
Author(s):  
Katsuhiko Matsui ◽  
Xiaolei Shi ◽  
Sayuko Komori ◽  
Atsumi Higuchi
Keyword(s):  
Topical Application ◽  
Langerhans Cells ◽  
Skin Lesions ◽  
Cell Development ◽  
Enzyme Linked Immunosorbent Assay ◽  
T Helper ◽  
Down Regulation ◽  
Th1 Cell ◽  
Th2 Cell ◽  
Helper Type

Background: It is well known that Langerhans cells (LCs) work as the primary orchestrators in polarization towards T helper type 1 (Th1) or T helper type 2 (Th2) immune responses. In this study, we examined the effects of various anti-allergy drugs against the Th2 cell development by LCs. Methods: The expression of cell surface molecules on LCs was investigated using reverse transcriptase polymerase chain reaction. The effects of anti-allergy drugs on T-cell immunoglobulin and mucin domain-containing protein (TIM)-4 expression in LCs were examined to predict whether they would inhibit Th2 cell development. Next, mice were primed via the hind footpad with ovalbumin (OVA)-pulsed LCs that had been treated with selected anti-allergy drugs. After 5 days, the cytokine response in the popliteal lymph nodes was investigated by enzyme-linked immunosorbent assay. The therapeutic effects of a selected drug on atopic dermatitis (AD) were assessed using AD-like skin lesions of NC/Nga mice. Results: The first-generation histamine H1 receptorantagonists, cyproheptadine and promethazine, and the second-generation histamine H1 receptor antagonists, emedastine and loratadine, were selected as candidate inhibitors of Th2 cell development. As expected, OVA peptide-pulsed LCs that had been treated with each drug and injected into the hind footpads of mice inhibited Th2 cell development, as represented by down-regulation of interleukin (IL)-4 production. Furthermore, the LCs that had been treated withemedastine also inhibited Th1 cell development, as represented by down-regulation of interferon (IFN)-g production. This additional inhibition of Th1 cell development was accompanied by suppression of CD40 expression in LCs. Therefore, the therapeutic effect of emedastine on AD was examined. Topical application of emedastine significantly suppressed the increase in the skin severity score in NC/Nga mice with AD-like skin lesions. This suppressive effect was associated with a decrease in the production of IFN-g and IL-4 in auricular lymph node cells. Conclusions: These results suggest that topical application of emedastine to skin lesions of patients with AD may provide clinical benefits through the inhibition of both Th1 cell and Th2 cell development mediated by LCs.

scholarly journals Topical Application of Doxycycline Inhibits Th2 Cell Development Mediated by Langerhans Cells and Exerts a Therapeutic Effect on Atopic Dermatitis

2020 ◽  
Vol 23 ◽  
pp. 86-99 ◽  
Author(s):  
Katsuhiko Matsui ◽  
Yuki Nojima ◽  
Yuka Kajiwara ◽  
Kana Busujima ◽  
Yuki Mori
Keyword(s):  
Atopic Dermatitis ◽  
Lymph Nodes ◽  
Topical Application ◽  
Severity Score ◽  
Langerhans Cells ◽  
Skin Lesions ◽  
Cell Development ◽  
Th2 Cells ◽  
Th2 Cytokines ◽  
Th2 Cell

Background: Langerhans cells (LCs) polarize the immune milieu towards a T helper type (Th) 1 or Th2 immune response. We investigated the effects of selected tetracyclines on Th cells development mediated by LCs, and their implications for the treatment of atopic dermatitis (AD). Methods: Mice were primed with ovalbumin (OVA) peptide-pulsed LCs, which had been treated with each antibiotic, via the hind footpad. After 5 days, the Th1/Th2 cytokine response in the popliteal lymph nodes was investigated by enzyme-linked immunosorbent assay. The expression of cell surface molecules on LCs was investigated using reverse transcriptase polymerase chain reaction. The therapeutic effects of a selected antibiotic on AD-like skin lesions of NC/Nga mice were assessed in terms of the skin severity score, histological changes in the lesioned skin, the serum level of total IgE, and expression of Th1/Th2 cytokines in lymph nodes and skin lesions. Results: Antibiotic-treated, OVA peptide-pulsed LCs inhibited development of Th2 cells but not Th1 cells. This was accompanied by suppression of T-cell immunoglobulin and mucin domain-containing protein (TIM)-4 expression in LCs. Doxycycline had the greatest activity against Staphylococcus aureus strains isolated from skin lesions of patients with AD, and a strong inhibitory effect on Th2 cell development. Doxycycline suppressed the increase in the skin severity score during the acute phase in NC/Nga mice similar to betamethasone. This suppressive effect was associated with a decrease in the serum IgE level and production of Th2 cytokines in auricular lymph node cells and skin lesions. Conclusion: Topical application of doxycycline to AD lesions would act on both superficial S. aureus colonization and epidermal LCs, thus possibly inhibiting the development of Th2 cells in vivo, with benefits for control of acute inflammation in AD.

scholarly journals Blimp-1 is essential for allergen-induced asthma and Th2 cell development in the lung

2020 ◽  
Vol 217 (7) ◽  
Author(s):  
Kun He ◽  
Angela Hettinga ◽  
Sagar Laxman Kale ◽  
Sanmei Hu ◽  
Markus M. Xie ◽  
...  
Keyword(s):  
Allergic Airway Inflammation ◽  
Cell Development ◽  
Th2 Cells ◽  
Th2 Response ◽  
Cell Responses ◽  
Th2 Cell ◽  
Th2 Immune Response ◽  
Upstream Promoter ◽  
Gata3 Expression ◽  
Anti Inflammatory Cytokine

A Th2 immune response is central to allergic airway inflammation, which afflicts millions worldwide. However, the mechanisms that augment GATA3 expression in an antigen-primed developing Th2 cell are not well understood. Here, we describe an unexpected role for Blimp-1, a transcriptional repressor that constrains autoimmunity, as an upstream promoter of GATA3 expression that is critical for Th2 cell development in the lung to inhaled but not systemically delivered allergens but is dispensable for TFH function and IgE production. Mechanistically, Blimp-1 acts through Bcl6, leading to increased GATA3 expression in lung Th2 cells. Surprisingly, the anti-inflammatory cytokine IL-10, but not the pro-inflammatory cytokines IL-6 or IL-21, is required via STAT3 activation to up-regulate Blimp-1 and promote Th2 cell development. These data reveal a hitherto unappreciated role for an IL-10–STAT3–Blimp-1 circuit as an initiator of an inflammatory Th2 response in the lung to allergens. Thus, Blimp-1 in a context-dependent fashion can drive inflammation by promoting rather than terminating effector T cell responses.

scholarly journals Blimp-1 is essential for Th2 cell development and allergic asthma

2019 ◽  
Author(s):  
Kun He ◽  
Angela Hettinga ◽  
Sagar Laxman Kale ◽  
Sanmei Hu ◽  
Markus M. Xie ◽  
...  
Keyword(s):  
Transcriptional Repressor ◽  
Allergic Airway Inflammation ◽  
Cell Development ◽  
Th2 Cells ◽  
Th2 Response ◽  
Cell Responses ◽  
Th2 Cell ◽  
Th2 Immune Response ◽  
Upstream Promoter ◽  
Gata3 Expression

AbstractA Th2 immune response is central to allergic airway inflammation, which afflicts millions worldwide. However, the mechanisms that augment GATA3 expression in an antigen-primed developing Th2 cell are not well understood. Here, we describe an unexpected role for Blimp-1, a transcriptional repressor that constrains autoimmunity, as an upstream promoter of GATA3 expression that is critical for Th2 cell development in the lung, but dispensable for TFH function and IgE production. Mechanistically, Blimp-1 acts through Bcl6, which is necessary to drive GATA3 expression. Surprisingly, the anti-inflammatory cytokine IL-10, but not the pro-inflammatory cytokines IL-6 or IL-21, is required via STAT3 activation to upregulate Blimp-1 and promote Th2 cell development. These data reveal a hitherto unappreciated role for an IL-10-STAT3-Blimp-1 circuit as an initiator of an inflammatory Th2 response in the lung to allergens. Thus, Blimp-1 in a context-dependent fashion can drive inflammation by promoting rather than terminating effector T cell responses.SummaryThe transcriptional repressor Blimp-1 acts via a pro-inflammatory IL-10-STAT3 axis as a critical positive regulator of Th2 cells in the lung in response to allergens driving pathophysiology associated with asthma disease.

scholarly journals Norfloxacin, a Fluoroquinolone Antibiotic, Inhibits Langerhans Cell-Mediated Th1 and Th2 Cell Development

2019 ◽  
Vol 22 ◽  
pp. 122-130 ◽  
Author(s):  
Katsuhiko Matsui ◽  
Azusa Kashima ◽  
Ayaka Motegi
Keyword(s):  
Topical Application ◽  
Skin Lesions ◽  
Cell Development ◽  
T Helper ◽  
Down Regulation ◽  
Th1 Cell ◽  
Th2 Cell ◽  
Fluoroquinolone Antibiotic ◽  
Th1 And Th2 ◽  
Helper Type

Background: It is widely acknowledged that Langerhans cells (LCs) play a primary role in the polarization of T helper type 1 (Th1) or T helper type 2 (Th2) immune responses. Our aim was to find fluoroquinolone (“new quinolone”) antibiotics that would inhibit LC-mediated Th2 cell development. Methods: Expression of LC surface molecules was investigated using the reverse transcriptase polymerase chain reaction. The effects of fluoroquinolone antibiotics on T-cell immunoglobulin and mucin domain-containing protein (TIM)-4 expression in LCs were examined to predict whether they would inhibit Th2 cell development. Mice were primed via the hind footpad with ovalbumin (OVA) peptide-pulsed LCs that had been treated with a selected fluoroquinolone antibiotic, then 5 days later the cytokine response in popliteal lymph nodes was examined by enzyme-linked immunosorbent assay. Results: Norfloxacin was selected as a candidate inhibitor of Th2 cell development. As expected, OVA peptide-pulsed LCs that had been treated with norfloxacin and injected into the hind footpads of mice inhibited Th2 cell development, as represented by down-regulation of interleukin (IL)-4 production, as well as Th1 cell development, as represented by down-regulation of interferon (IFN)- g production. This additional inhibition of Th1 cell development was accompanied by suppression of CD40 expression in LCs. In addition, Staphylococcus aureus strains isolated from skin lesions of patients with atopic dermatitis (AD) were more susceptible to norfloxacin than to gentamicin. Topical treatment with norfloxacin significantly suppressed the increase in the skin severity score in NC/Nga mice with AD-like skin lesions. This suppressive effect was associated with a decrease in the production of IFN-g and IL-4 in auricular lymph node cells. Conclusions: The present results show that topical application of norfloxacin inhibits the development of AD-like skin lesions in NC/Nga mice. This suggests that topical application of norfloxacin to AD lesions colonized with S. aureus would act on both superficial S. aureus and epidermal LCs, thus possibly inhibiting the development of Th1 and Th2 cells in vivo, and controlling the severity of AD.

scholarly journals Differentiation and stability of T helper 1 and 2 cells derived from naive human neonatal CD4+ T cells, analyzed at the single-cell level.

1996 ◽  
Vol 184 (2) ◽  
pp. 473-483 ◽  
Author(s):  
T Sornasse ◽  
P V Larenas ◽  
K A Davis ◽  
J E de Vries ◽  
H Yssel
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
Cd4 T Cells ◽  
Biological Activities ◽  
Th2 Cells ◽  
Cell Phenotype ◽  
T Helper ◽  
Th1 Cell ◽  
Th2 Cell ◽  
Th1 And Th2

The development of CD4+ T helper (Th) type 1 and 2 cells is essential for the eradication of pathogens, but can also be responsible for various pathological disorders. Therefore, modulation of Th cell differentiation may have clinical utility in the treatment of human disease. Here, we show that interleukin (IL) 12 and IL-4 directly induce human neonatal CD4- T cells, activated via CD3 and CD28, to differentiate into Th1 and Th2 subsets. In contrast, IL-13, which shares many biological activities with IL-4, failed to induce T cell differentiation, consistent with the observation that human T cells do not express IL-13 receptors. Both the IL-12-induced Th1 subset and the IL-4-induced Th2 subset produce large quantities of IL-10, confirming that human IL-10 is not a typical human Th2 cytokine. Interestingly, IL-4-driven Th2 cell differentiation was completely prevented by an IL-4 mutant protein (IL-4.Y124D), indicating that this molecule acts as a strong IL-4 receptor antagonist. Analysis of single T cells producing interferon gamma or IL-4 revealed that induction of Th1 cell differentiation occurred rapidly and required only 4 d of priming of the neonatal CD4+ T cells in the presence of IL-12. The IL-12-induced Th1 cell phenotype was stable and was not significantly affected when repeatedly stimulated in the presence of recombinant IL-4. In contrast, the differentiation of Th2 cells occurred slowly and required not only 6 d of priming, but also additional restimulation of the primed CD4+ T cells in the presence of IL-4. Moreover, IL-4-induced Th2 cell phenotypes were not stable and could rapidly be reverted into a population predominantly containing Th0 and Th1 cells, after a single restimulation in the presence of IL-12. The observed differences in stability of IL-12- and IL-4-induced human Th1 and Th2 subsets, respectively, may have implications for cytokine-based therapies of chronic disease.

scholarly journals Mast Cells Stimulated with Peptidoglycan from Staphylococcus aureus Augment the Development of Th1 Cells

2018 ◽  
Vol 21 ◽  
pp. 296-304
Author(s):  
Katsuhiko Matsui ◽  
Saeko Kanai ◽  
Manami Ikuta ◽  
Saki Horikawa
Keyword(s):  
Staphylococcus Aureus ◽  
Mast Cells ◽  
Chronic Inflammation ◽  
Cell Development ◽  
Th1 Cells ◽  
T Helper ◽  
Th1 Cell ◽  
Th Cells ◽  
Th2 Cell ◽  
Helper Type

Background: The skin of patients with atopic dermatitis (AD) is superficially colonized by Staphylococcus aureus. We have previously found that percutaneous permeation of peptidoglycan (PEG) from S. aureus increases the number of mast cells in the dermis, as seen in skin lesions of AD patients. The purpose of the present study was to clarify the influence of PEG on T helper type 1 (Th1)/ T helper type 2 (Th2) cell development mediated by mast cells. Methods: Mast cells were induced by long-term culture of murine spleen cells in medium supplemented with tumor necrosis factor (TNF)- a. Ovalbumin (OVA) peptide-pulsed mast cells were incubated with naïve Th cells in the presence or absence of PEG. Five days later, Th cells in the culture were stimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin, and Th1/Th2 cytokine production was investigated by enzyme-linked immunosorbent assay. Results: It was confirmed that the mast cells we obtained had surface expression of I-Ad, worked as antigen-presenting cells, and induced Th1 cell and Th2 cell development. The stimulation of mast cells with PEG enhanced the development of Th1 cells but not that of Th2 cells. The increase of Th1 cell development stimulated by PEG was associated with an increase in the expression of Notch ligand Delta 1 in the mast cells. Furthermore, treatment of mast cells with the macrolide antibiotic josamycin suppressed Th1 cell development and this was correlated with a reduction of both Delta 1 expression and interleukin (IL)-12 production in mast cells. Conclusions: Colonization of S. aureus on the lesioned skin of AD patients contributes to not only an increase in the number of mast cells but also Th1 cell development mediated by mast cells in the dermis and subsequent induction of chronic inflammation, which is characterized by up-regulation of the Th1 cytokine, interferon (IFN)- g. Therefore, application of josamycin to the lesional skin of AD patients may provide relief from chronic inflammation mediated by mast cells.

GATA-3 Requires C-Myb to Auto-Regulate Its Own Expression in Normal Human Peripheral Blood Lymphocytes Undergoing T Helper Type 2 (Th2) Cell Development

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2575-2575
Author(s):  
Yuji Nakata ◽  
Shenghao Jin ◽  
Yuan Shen ◽  
Alan M. Gewirtz
Keyword(s):  
T Cells ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Human Peripheral Blood ◽  
Cell Formation ◽  
Cell Development ◽  
Peripheral Blood Lymphocytes ◽  
T Helper ◽  
Th1 Cell ◽  
Th2 Cell

Abstract The c-myb protooncogene encodes a transcription factor, c-Myb, which is highly expressed in immature hematopoietic cells. c-Myb is required for many critical aspects of blood cell development including lineage fate selection, proliferation, and at multiple time points during early myeloid, and B and T lymphoid cell development. GATA-3, which belongs to a family of zinc finger transcription factors, is also required at several steps in early T cell development, and specifically in regard to this communication, for the development of T helper type 2 (Th2) cells. A recent study by Maurice et al (EMBO2007, 26:3629–3640) reported that c-myb regulates T helper cell lineage commitment in developing mouse thymocytes via regulation of GATA-3 expression. As we were unaware of any studies that have addressed the role of c-Myb and GATA-3 in normal human peripheral blood lymphocytes (PBL), we explored the potential regulatory relationship between these transcription factors in cells of this type. Proceeding from the murine studies, we performed a chromatin immunoprecipitation assay (ChIP) which showed that c-Myb bound the GATA-3 downstream promoter in naïve CD4+ T cells under conditions designed to promote Th2 growth. Such binding was not observed in cells stimulated under Th1 promoting conditions. The interaction of c-Myb and GATA-3 proteins was also detected in cell lysates under Th2 cell promoting conditions by immunoprecipitation with both anti-c-Myb, and anti-GATA-3 polyclonal antibodies. Of note, immunoprecipitation with these same antibodies did not show binding of either protein to STAT6. Additional studies revealed that c-Myb activated a GATA-3 minimal promoter by direct binding to a conserved c-Myb binding site in peripheral blood T cells. Of even greater interest, in 293T cells, GATA-3 activated its own promoter ~6 fold when c-Myb was co-expressed in 293T cells. In the absence of c-Myb, GATA-3 did not significantly activate its own promoter in these cells. We have recently shown that c-Myb binds to MLL via menin. A ChIP assay also showed that MLL and Menin bound to the GATA-3 promoter suggesting that c-Myb and GATA-3 form a co-activator complex on the GATA-3 promoter with MLL. Finally, to explore the role of c-myb expression in human peripheral blood naive CD4+ T cells, we employed c-Myb targeted, and control, short hairpin RNA (shRNA) expressed from a lentivirus vector. This strategy yielded a sequence specific 80–90% knockdown of c-Myb expression in our hands. Stimulation of naive peripheral blood CD4+ T cells expressing the c-Myb directed shRNA with cytokines promoting Th2 cell formation (IL-4, IL-2, and anti-IL-12 antibody) blocked the up-regulation of GATA-3 mRNA expression ~90% compared to cells in which a control shRNA had been expressed. Flow cytometric analysis revealed that intracellular IL-4 expression also was diminished. In contrast, silencing c-myb had no effect on T-bet mRNA expression, or intracellular interferon-expression in the cells induced to undergo Th1 cell formation with IL-12, IL-2 and anti-IL-4 antibody. We conclude from these studies that c-Myb regulates developmental programs specific for Th2, as opposed to Th1, cell development. We hypothesize that such control is exerted in peripheral blood T lymphocytes, at least in part, through direct control of GATA-3, whose expression is auto-regulated with the assistance of c-Myb, and perhaps MLL, acting as transcriptional co-factors.

scholarly journals Development of the Th2 Immune Response Models to Evaluate Allergenicity of Milk Proteins

2021 ◽  
Author(s):  
◽  
Marcus James Robinson
Keyword(s):  
Immune Response ◽  
Mast Cell ◽  
Allergic Disease ◽  
Milk Proteins ◽  
Goat Milk ◽  
Cell Development ◽  
Th2 Cells ◽  
Th2 Cell

<p>Food allergy, defined as an adverse immune response to food, is increasing in prevalence. It can be broadly separated into phases of sensitization, in which allergy-triggering Immunoglobulin E (IgE) is generated, and the post-sensitization allergic response, in which the allergic response is triggered by sensitizing allergen. While much is known about the specific mediators that cause allergies, the immune processes that underlie disease progression are less clear. This project has employed mouse models of Th2 immunity to clarify the factors involved in the initiation and maintenance of allergic disease.  At the centre of allergic disease is the Interleukin (IL)-4-producing CD4+ T helper type 2 (Th2) cell. One of the key inducers of Th2 cell development in vitro is IL-4, but its involvement in Th2 cell development in vivo is controversial. In our studies, we saw that Th2 cell development could be initiated in vivo by primary, adjuvant-free allergen immunisation in the absence of IL-4. However, Th2 cells were more frequent in IL-4-sufficient conditions. We also determined that genetic lesions that result in loss of one, or both, IL-4 alleles impaired the Th2 cell-mediated allergic process, such that IL-4-heterozygous mice can be considered haplo-insufficient for IL-4 in allergic disease contexts.  In addition to the generation of IgE antibody, Th2 cells are implicated in the post-sensitization phase of allergy. Multiple oral challenges of sensitized mice induces elevations in Th2-associated cytokines and elevates intestinal mast cell frequencies. It was the second aim of this project to clarify the role of CD4+ T cells in the post-sensitization intestinal allergic process. We demonstrate a key role for CD4+ T cells in this jejunal mast cell recruitment, and identify that this is required in addition to their established contribution to IgE production. Our investigations also reveal a previously unappreciated role for the CD4+ T cell-derived cytokine IL-3 in oral food allergy. These findings suggest that intestinally localised mast cell-inducer Th2 (Th2m) cells are required for allergic responses generated in the intestine. We also investigated whether specific components of ruminant milks influence the allergic process. While goat and cow milks share significant protein homology, goat milk has lower sensitizing and response-evoking capacity, or allergenicity, than cow milk, in numerous experimental systems. In this project, we compared dominant allergens purified from cow and goat milks for their ability to initiate Th2 cell development. We also examined the ability of one of these allergens to initiate the intestinal allergic process. In these studies, we observed similar Th2 cell development and intestinal mast cell activity in response to both cow and goat milk proteins. These responses indicate that the intrinsic allergenicity of the proteins analysed is not sufficient to explain the differential allergenicity attributed to cow and goat milk.  These studies examine the endogenous and exogenous factors that contribute to the development of allergic disease. This project clarifies the role of IL-4 in in vivo Th2 cell development, identifies functional segregation of CD4+ Th2 cells in the intestinal allergic process and further illustrates some of the similarities in the allergenicity of isolated cow and goat milk proteins. Collectively, these studies uncover fundamental aspects of the allergic process which may be useful targets for disease intervention in both prophylactic and therapeutic settings.</p>

scholarly journals Distinct Role of Antigen-Specific T Helper Type 1 (Th1) and Th2 Cells in Tumor Eradication in Vivo

1999 ◽  
Vol 190 (5) ◽  
pp. 617-628 ◽  
Author(s):  
Takashi Nishimura ◽  
Kenji Iwakabe ◽  
Masashi Sekimoto ◽  
Yasushi Ohmi ◽  
Takashi Yahata ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Th2 Cells ◽  
T Helper ◽  
Th1 Cell ◽  
Th2 Cell ◽  
Tumor Eradication ◽  
Th1 And Th2

The role of T helper type 1 (Th1) and Th2 cells in tumor immunity was investigated using Th cells induced from ovalbumin (OVA)-specific T cell receptor transgenic mice. Although Th1 cells exhibited stronger cytotoxicity than Th2 cells, both cell types completely eradicated tumors when transferred into mice bearing A20 tumor cells transfected with the OVA gene (A20-OVA). Th1 cells eradicated the tumor mass by inducing cellular immunity, whereas Th2 cells destroyed the tumor by inducing tumor necrosis. Both Th1 and Th2 cells required CD8+ T cells to eliminate tumors, and neither of these cells were able to completely eliminate A20-OVA tumors from T and B cell–deficient RAG2−/− mice. Mice cured from tumors by Th1 and Th2 cell therapy rejected A20-OVA upon rechallenge, but CD8+ cytotoxic T lymphocytes were induced only from spleen cells prepared from cured mice by Th1 cell therapy. Moreover, we demonstrated that Th1 and Th2 cells used distinct adhesion mechanisms during tumor eradication: the leukocyte function-associated antigen (LFA)-1–dependent cell–cell adhesion step was essential for Th1 cell therapy, but not for Th2 cell therapy. These findings demonstrated for the first time the distinct role of antigen-specific Th1 and Th2 cells during eradication of established tumors in vivo.

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