Do studies in humans better depict Th17 cells?

Blood ◽  
2009 ◽  
Vol 114 (11) ◽  
pp. 2213-2219 ◽  
Author(s):  
Francesco Annunziato ◽  
Sergio Romagnani
Keyword(s):  
Th17 Cells ◽  
Transforming Growth Factor ◽  
Heterogeneous Population ◽  
Th2 Cells ◽  
Th1 Cells ◽  
T Helper ◽  
Unique Ability ◽  
Th Lymphocytes

Abstract CD4+ T helper (Th) lymphocytes represent a heterogeneous population of cells. In addition to type 1 (Th1) and type 2 (Th2) cells, another subset of CD4+ effector Th cells has been discovered and named as Th17, because of its unique ability to produce interleukin (IL)–17. Studies in mice initially suggested that Th17 cells are the pathogenic cells in autoimmune disorders, whereas Th1 cells may behave rather as protective. Subsequent studies in humans demonstrated the plasticity of Th17 cells and their possibility to shift to Th1. The plasticity of Th17 to Th1 cells has recently been confirmed in mice, where it was found that Th17 cells seem to be pathogenic only when they shift to Th1 cells. Studies in humans also showed that Th17 cells are different than in mice because all of them express CD161 and exclusively originate from CD161+ precursors present in umbilical cord blood and newborn thymus. While murine Th17 cells develop in response to IL-6, IL-1, and transforming growth factor (TGF)–β, human Th17 cells originate from these CD161+ precursors in response to IL-1β and IL-23, the need for TGF-β being controversial. Thus, we believe that studies in humans have better depicted human Th17 cells than studies in mice.

scholarly journals T Helper Type 2 Cell Differentiation Occurs in the Presence of Interleukin 12 Receptor β2 Chain Expression and Signaling

2000 ◽  
Vol 191 (5) ◽  
pp. 847-858 ◽  
Author(s):  
Ryuta Nishikomori ◽  
Rolf O. Ehrhardt ◽  
Warren Strober
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Th2 Cells ◽  
Interleukin 12 ◽  
Th1 Cells ◽  
T Helper ◽  
Ifn Γ ◽  
Helper Type

The differentiation of CD4+ T cells into T helper type 1 (Th1) cells is driven by interleukin (IL)-12 through the IL-12 receptor β2 (IL-12Rβ2) chain, whereas differentiation into Th2 cells is driven by IL-4, which downregulates IL-12Rβ2 chain. We reexamined such differentiation using IL-12Rβ2 chain transgenic mice. We found that CD4+ T cells from such mice were able to differentiate into Th2 cells when primed with IL-4 or IL-4 plus IL-12. In the latter case, the presence of IL-4 suppressed interferon (IFN)-γ production 10–100-fold compared with cells cultured in IL-12 alone. Finally, in studies of the ability of IL-12 to convert Th2 cells bearing a competent IL-12R to the Th1 cells, we showed that: (a) T cells bearing the IL-12Rβ2 chain transgene and primed under Th2 conditions could not be converted to Th1 cells by repeated restimulation under Th1 conditions; and (b) established Th2 clones transfected with the IL-12Rβ2 chain construct continued to produce IL-4 when cultured with IL-12. These studies show that IL-4–driven Th2 differentiation can occur in the presence of persistent IL-12 signaling and that IL-4 inhibits IFN-γ production under these circumstances. They also show that established Th2 cells cannot be converted to Th1 cells via IL-12 signaling.

scholarly journals Th2 cells are less susceptible than Th1 cells to the suppressive activity of CD25+ regulatory thymocytes because of their responsiveness to different cytokines

Blood ◽  
2004 ◽  
Vol 103 (8) ◽  
pp. 3117-3121 ◽  
Author(s):  
Lorenzo Cosmi ◽  
Francesco Liotta ◽  
Roberta Angeli ◽  
Benedetta Mazzinghi ◽  
Veronica Santarlasci ◽  
...  
Keyword(s):  
Treg Cells ◽  
Suppressive Effect ◽  
Interleukin 4 ◽  
Th2 Cells ◽  
Th1 Cells ◽  
Suppressive Activity ◽  
T Helper ◽  
Cell Clones

Abstract T-cell clones generated from both CD4+CD25+ and CD8+CD25+ human thymocytes were assessed for their ability to suppress the proliferative response to allogeneic stimulation of type 1 T-helper (Th1) or type 2 T-helper (Th2) clones derived from autologous CD4+CD25- thymocytes. Both CD4+ and CD8+ T-regulatory (Treg) cells completely suppressed the proliferation of Th1 clones but exhibited significantly lower suppressive activity on the proliferation of Th2 clones. The partial suppressive effect on Th2 cells was further reduced by the addition in culture of interleukin-4 (IL-4), whereas it was increased in the presence of an anti–IL-4 monoclonal antibody (mAb). The suppressive activity on Th2 clones was also completely inhibited by the addition of IL-7, IL-9, and IL-15 but not of IL-2, whereas the suppressive effect on Th1 clones was only reverted by the addition of IL-15. Of note, Th2 clones expressed significantly higher amounts of mRNA for IL-4 receptor (IL-4R) and IL-9R α chains than Th1 clones, whereas the expression of mRNA for IL-2R, IL-7R, and IL-15R α chains was comparable. Taken together, these findings demonstrate that Th2 cells have a lower susceptibility than Th1 cells to the suppressive activity of human CD25+ regulatory thymocytes, because they are able to produce, and to respond to, growth factors distinct from IL-2, such as IL-4 and IL-9. (Blood. 2004; 103:3117-3121)

scholarly journals Critical Involvement of CD44 in T Helper Type 2 Cell-Mediated Eosinophilic Airway Inflammation in a Mouse Model of Acute Asthma

2022 ◽  
Vol 12 ◽  
Author(s):  
Shigeki Katoh
Keyword(s):  
Monoclonal Antibodies ◽  
Airway Inflammation ◽  
Th17 Cells ◽  
Acute Asthma ◽  
Mite Allergen ◽  
Th2 Cells ◽  
T Helper ◽  
Th2 Cell ◽  
Helper Type

Interactions between CD44 and hyaluronan (HA) are crucial for recruiting leukocytes to inflamed tissues. This review summarizes findings from our studies of the roles of CD44-HA interactions in leukocyte trafficking, with a particular focus on airway T helper type 2 (Th2) cells in mouse models of acute asthma. In a mite allergen-induced model of acute asthma, intraperitoneal injection of anti-CD44 monoclonal antibodies blocked lymphocytes and eosinophils from accumulating in the lung, and suppressed both the antigen-induced increase in Th2 cytokines in the bronchoalveolar lavage fluid (BALF) and airway hyperresponsiveness (AHR). CD44 deficiency was associated with decreased mite allergen-induced Th2 cell-mediated airway inflammation and AHR in sensitized mice. Asthmatic responses to antigen-sensitized splenic CD4+ T cells transferred from CD44-deficient mice were weaker than in wild-type mice. Administration of anti-CD44 monoclonal antibodies preferentially suppressed the airway accumulation of antigen-specific Th2 cells induced by antigen challenge, without affecting Th1 and Th17 cells. Increased HA-binding ability of CD44 and expression of Neu1 sialidase were observed on antigen-specific Th2 cells compared with antigen-specific Th1 and Th17 cells. Finally, in a mouse model of acute asthma, neuraminidase 1-deficient SM/J mice exhibited a lower Th2 cytokine concentration and a lower absolute Th2 cell number in the BALF, as well as an attenuated AHR. Our findings indicate that CD44 critically contributes to the antigen challenge-induced airway accumulation of antigen-specific Th2 cells, without affecting Th1 and Th17 cells, in mice. Furthermore, neuraminidase 1 activity is necessary for the interaction between HA and CD44, and Th2 cell-mediated airway inflammation.

scholarly journals T-bet regulates Th1 responses through essential effects on GATA-3 function rather than on IFNG gene acetylation and transcription

2006 ◽  
Vol 203 (3) ◽  
pp. 755-766 ◽  
Author(s):  
Takashi Usui ◽  
Jan C. Preiss ◽  
Yuka Kanno ◽  
Zheng Ju Yao ◽  
Jay H. Bream ◽  
...  
Keyword(s):  
Early Stage ◽  
Th2 Cells ◽  
Th1 Cells ◽  
T Helper ◽  
Down Regulation ◽  
Ifng Gene ◽  
Deoxyribonuclease I ◽  
Negative Effect ◽  
Th2 Differentiation

T helper type 1 (Th1) development is facilitated by interrelated changes in key intracellular factors, particularly signal transducer and activator of transcription (STAT)4, T-bet, and GATA-3. Here we show that CD4+ cells from T-bet−/− mice are skewed toward Th2 differentiation by high endogenous GATA-3 levels but exhibit virtually normal Th1 differentiation provided that GATA-3 levels are regulated at an early stage by anti–interleukin (IL)-4 blockade of IL-4 receptor (R) signaling. In addition, under these conditions, Th1 cells from T-bet−/− mice manifest IFNG promotor accessibility as detected by histone acetylation and deoxyribonuclease I hypersensitivity. In related studies, we show that the negative effect of GATA-3 on Th1 differentiation in T-bet−/− cells arises from its ability to suppress STAT4 levels, because if this is prevented by a STAT4-expressing retrovirus, normal Th1 differentiation is observed. Finally, we show that retroviral T-bet expression in developing and established Th2 cells leads to down-regulation of GATA-3 levels. These findings lead to a model of T cell differentiation that holds that naive T cells tend toward Th2 differentiation through induction of GATA-3 and subsequent down-regulation of STAT4/IL-12Rβ2 chain unless GATA-3 levels or function is regulated by T-bet. Thus, the principal function of T-bet in developing Th1 cells is to negatively regulate GATA-3 rather than to positively regulate the IFNG gene.

scholarly journals A critical role for transforming growth factor-beta but not interleukin 4 in the suppression of T helper type 1-mediated colitis by CD45RB(low) CD4+ T cells.

1996 ◽  
Vol 183 (6) ◽  
pp. 2669-2674 ◽  
Author(s):  
F Powrie ◽  
J Carlino ◽  
M W Leach ◽  
S Mauze ◽  
R L Coffman
Keyword(s):  
T Cells ◽  
Growth Factor ◽  
Cd4 T Cells ◽  
Transforming Growth Factor ◽  
Th2 Cells ◽  
Tgf Beta ◽  
T Helper ◽  
Cd4 Cells ◽  
Helper Type

A T helper type 1 (Th1)-mediated colitis with similarities to inflammatory bowel disease in humans developed in severe combined immunodeficiency mice reconstituted with CD45RB(high) CD4+ splenic T cells and could be prevented by cotransfer of CD45RB(low) CD4+ T cells. Inhibition of this Th1 response by the CD45RB(low) T cell population could be reversed in vivo by an anti-transforming growth factor (TGF) beta antibody. Interleukin (IL) 4 was not required for either the differentiation of function of protective cells as CD45RB(low) CD4+ cells from IL-4-deficient mice were fully effective. These results identify a subpopulation of peripheral CD4+ cells and TGF-beta as critical components of the natural immune regulatory mechanism, which prevents the development of pathogenic Th1 responses in the gut, and suggests that this immunoregulatory population is distinct from Th2 cells.

Subsets and Function Changes of Th Cells in the Bone Marrow of Patients with Immune Related Pancytopenia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3762-3762
Author(s):  
Guangsheng He ◽  
Xiuli Wang ◽  
De Pei Wu ◽  
Aining Sun ◽  
Zhengming Jin
Keyword(s):  
Bone Marrow ◽  
Mononuclear Cells ◽  
Th2 Cells ◽  
Th1 Cells ◽  
T Helper ◽  
Ifn Γ ◽  
Polymerase Chain ◽  
And Function ◽  
Normal Controls ◽  
Th Lymphocytes

Abstract Objectives To explore the subsets and function of T helper (Th) in bone marrow of the patients with immune related pancytopenia(IRP). Methods The CD4+ cells producing IFN-γ or IL-4 in cytoplasm were defined as Th1 or Th2 cells respectively. All these cells in bone marrow were measured from 16 normal controls, 25 untreated IRP patients; The mRNA expressions of IL-4, IL-10, IFN-γ and IL-2 genes in unstimulated bone marrow mononuclear cells(BMMNC)from 25 untreated IRP patients, 10 normal controls were measured by reverse transcription polymerase chain reaction (RT-PCR). Results The percentage of Th1 cells, Th2 cells and ratio of Th1/Th2 in bone marrow of normal controls was: 0.42%, 0.24%, 1.57 respectively, and the percentage of Th1 cells in untreated patients with IRP was 0.58%, which was not markedly different from the that of normal controls(t=0.903, P>0.05). But the percentage of Th2 cells of the patients with IRP was significantly higher than that of normal controls(t=4.673, P<0.01), and the balance of Th1/Th2 shifted to Th2 more significantly by comparing to that of normal controls (t=4.880, P<0.01). The mRNA expressions of IL-4 and IL-10 in the Th2 cells of the untreated IRP patients were significantly higher than those of the normal controls, however difference of the expressions of IFN-γ and IL-2 in the Th1 cells were not significantly. Conclusions The percentage of Th2 cells increased in the patients with IRP, and the balance of Th1/Th2 shifted to Th2. And the expression of Th2 type cytokines was more frequent in IRP. The imbalance of subtypes of Th lymphocytes and hyperfunction of Th2 lymphocytes might play important roles in the pathogenic mechanism of IRP, which lead to more B lymphocytes and producing autoantibodies consistenly.

scholarly journals T Helper 17 Cells in Autoimmune Liver Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Masanori Abe ◽  
Yoichi Hiasa ◽  
Morikazu Onji
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Autoimmune Diseases ◽  
Th17 Cells ◽  
Transforming Growth Factor ◽  
Treg Cells ◽  
Reciprocal Relationship ◽  
Th2 Cells ◽  
T Helper ◽  
T Helper 17

Many autoimmune diseases are driven by self-reactive T helper (Th) cells. A new population of effector CD4+T cells characterized by the secretion of interleukin (IL)-17, referred to as Th17 cells, has been demonstrated to be phenotypically, functionally, and developmentally distinct from Th1 and Th2 cells. Because the liver is known to be an important source of transforming growth factor-βand IL-6, which are cytokines that are crucial for Th17 differentiation, it is very likely that Th17 cells contribute to liver inflammation and autoimmunity. In contrast, another distinct subset of T cells, regulatory T cells (Treg), downregulate immune responses and play an important role in maintaining self-tolerance. In addition, there is a reciprocal relationship between Th17 cells and Tregs, in development and effector functions, and the balance between Th17 and Treg cells can affect the outcome of immune responses, particularly in autoimmune diseases. In this review, we will focus on the latest investigative findings related to Th17 cells in autoimmune liver disease.

scholarly journals Negative air ion exposure ameliorates depression-like behaviors induced by chronic mild stress in mice

2021 ◽  
Author(s):  
Yunqing Hu ◽  
Tingting Niu ◽  
Jianming Xu ◽  
Li Peng ◽  
Qinghua Sun ◽  
...  
Keyword(s):  
Chronic Mild Stress ◽  
Psychological Status ◽  
Th2 Cells ◽  
Depression Symptoms ◽  
Mild Stress ◽  
T Helper ◽  
Alternative Approach ◽  
Immobility Time

Abstract The presence of negative air ions (NAI) is suggested to be a good factor in improving psychological status and used in treating depression as an alternative approach. However, the biological explanation for effects of NAI on alleviating depression symptoms has less been explored. In this study, the chronic mild stress (CMS) protocol was used to induce transcriptional depressive-like behaviors in mice, and the effects of NAI exposure on CMS-induced depression-like behaviors were examined. Thirty-day NAI exposure prevented the CMS-induced depression-like behaviors as shown by the restoration of sucrose preference and reduced immobility time in the suspension test. In addition, the elevation of serous corticosterone was present in CMS-treated mice but not existed in those with the NAI exposure. Furthermore, we observed a shifted balance between the cytokines secreted by type 1 T helper (Th1) cells and type 2 T helper (Th2) cells. In conclusion, NAI intervention is able to ameliorate CMS-induced depression-like behaviors in mice, and this effect is associated with the alteration of corticosterone and functional rebalance between Th1 and Th2 cells.

scholarly journals Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides

2006 ◽  
Vol 203 (10) ◽  
pp. 2271-2279 ◽  
Author(s):  
Spencer C. Liang ◽  
Xiang-Yang Tan ◽  
Deborah P. Luxenberg ◽  
Riyez Karim ◽  
Kyriaki Dunussi-Joannopoulos ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Th17 Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Th2 Cells ◽  
T Helper ◽  
Distinct Lineage ◽  
Th 1

Th17 cells are a distinct lineage of effector CD4+ T cells characterized by their production of interleukin (IL)-17. We demonstrate that Th17 cells also expressed IL-22, an IL-10 family member, at substantially higher amounts than T helper (Th)1 or Th2 cells. Similar to IL-17A, IL-22 expression was initiated by transforming growth factor β signaling in the context of IL-6 and other proinflammatory cytokines. The subsequent expansion of IL-22–producing cells was dependent on IL-23. We further demonstrate that IL-22 was coexpressed in vitro and in vivo with both IL-17A and IL-17F. To study a functional relationship among these cytokines, we examined the expression of antimicrobial peptides by primary keratinocytes treated with combinations of IL-22, IL-17A, and IL-17F. IL-22 in conjunction with IL-17A or IL-17F synergistically induced the expression of β-defensin 2 and S100A9 and additively enhanced the expression of S100A7 and S100A8. Collectively, we have identified IL-22 as a new cytokine expressed by Th17 cells that synergizes with IL-17A or IL-17F to regulate genes associated with skin innate immunity.

scholarly journals CD28-induced costimulation of T helper type 2 cells mediated by induction of responsiveness to interleukin 4.

1993 ◽  
Vol 178 (5) ◽  
pp. 1645-1653 ◽  
Author(s):  
J G McArthur ◽  
D H Raulet
Keyword(s):  
Interleukin 2 ◽  
Interleukin 4 ◽  
Th2 Cells ◽  
T Helper ◽  
Autocrine Growth ◽  
Th Cells ◽  
Antigen Presenting ◽  
Helper Type

Type 1 and type 2 cloned T helper (Th) cells are believed to require different antigen-presenting cell (APC)-derived costimuli for proliferation. In the case of Th1-cloned T cells, CD28 signaling costimulates production of autocrine interleukin 2 (IL-2). Th2 cells produce their autocrine growth factor, IL-4, without costimulation, but require APC-derived costimuli, or IL-1, to respond to IL-4. Here we demonstrate that engagement of CD28 on Th2 cells with anti-CD28 antibody or with APC-associated B7 costimulates Th2 responsiveness to IL-4 but does not affect IL-4 or IL-2 production by Th2 cells. Costimulation of Th2 cells via CD28 appears to involve the induction of IL-1 production by Th2 cells, which acts in an autocrine fashion to induce IL-4 responsiveness. These results suggest that CD28-induced costimulation plays an important role in responses mediated by both types of Th cells.

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