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 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.

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.

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-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 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.

Interleukin-4-dependent induction of preproenkephalin in antigen-specific T helper-type 2 (Th2) cells

2000 ◽  
Vol 105 (2) ◽  
pp. 103-108 ◽  
Author(s):  
Takashi Yahata ◽  
Chie Yahata ◽  
Akio Ohta ◽  
Masashi Sekimoto ◽  
Hidemitsu Kitamura ◽  
...  
Keyword(s):  
Interleukin 4 ◽  
Th2 Cells ◽  
T Helper ◽  
Helper Type

scholarly journals Early Growth Response Protein-1 (Egr-1) Is Preferentially Expressed in T Helper Type 2 (Th2) Cells and Is Involved in Acute Transcription of the Th2 Cytokine Interleukin-4

2009 ◽  
Vol 285 (3) ◽  
pp. 1643-1652 ◽  
Author(s):  
Michael Lohoff ◽  
Marco Giaisi ◽  
Rebecca Köhler ◽  
Bärbel Casper ◽  
Peter H. Krammer ◽  
...  
Keyword(s):  
Growth Response ◽  
Early Growth ◽  
Interleukin 4 ◽  
Th2 Cells ◽  
T Helper ◽  
Early Growth Response ◽  
Th2 Cytokine ◽  
Helper Type

scholarly journals Genetic Control of Schistosome Infections by the SM1 Locus of the 5q31-q33 Region Is Linked to Differentiation of Type 2 Helper T Lymphocytes

1999 ◽  
Vol 67 (9) ◽  
pp. 4689-4692 ◽  
Author(s):  
Virmondes Rodrigues ◽  
Karen Piper ◽  
Patricia Couissinier-Paris ◽  
Olivia Bacelar ◽  
Hélia Dessein ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
T Cell Differentiation ◽  
Interleukin 4 ◽  
Helper T Lymphocytes ◽  
Cell Clones ◽  
Patient Groups ◽  
Homozygous Resistant

ABSTRACT Human susceptibility to Schistosoma mansoni infections is controlled by the SM1 locus on chromosome 5 in q31-q33. This genetic region encodes cytokines which regulate the development of helper T lymphocytes. In the present work, a clonal analysis of CD4+T lymphocytes of homozygous resistant and homozygous susceptible subjects was undertaken to evaluate whether SM1 controls helper T-cell differentiation. Of 121 CD4+ T-cell clones (TCC) from three susceptible (S) and three resistant (R) subjects, 68 proliferated when stimulated by parasite antigens. Parasite-specific TCC derived from susceptible subjects (33 STCC) produced 10- to 1,000-fold less interleukin-4 and -5 than TCC from resistant subjects (25 RTCC). Clones from both patient groups produced, however, the same amount of gamma interferon. Parasite-specific STCC were type 1 helper (Th1) or Th0/1, whereas RTCC were either Th2 or Th0/2. These results, together with the localization of SM1 in 5q31-q33, indicate that the SM1 locus controls the differentiation of Th2 lymphocytes.

scholarly journals Impaired Interleukin 4 Signaling in T Helper Type 1 Cells

1998 ◽  
Vol 187 (8) ◽  
pp. 1305-1313 ◽  
Author(s):  
Hua Huang ◽  
William E. Paul
Keyword(s):  
T Cells ◽  
Janus Kinase ◽  
Interleukin 4 ◽  
Insulin Receptor Substrate ◽  
Th1 Cells ◽  
T Helper ◽  
Protein Levels ◽  
The Stability ◽  
Altered Sensitivity

Cluster of differentation (CD)4+ T helper cells (Th)1s fail to produce interleukin (IL)-4. Even if restimulated in the presence of IL-4, a condition that induces IL-4–producing capacity in naive CD4+ T cells, Th1s fail to become IL-4 producers. We report that Th1 cells have a major impairment in IL-4 signaling. When compared to both Th2s and naive T cells, they display a striking diminution in phosphorylation of Stat6. They also show reduced phosphorylation of Janus kinase (JAK)-3 and insulin receptor substrate (IRS)-2 when compared to Th2s. Stat6 and JAK-3 are present in equivalent amounts in Th1s and Th2s, but IRS-2 protein levels are much lower in Th1s than in Th2s. Altered sensitivity to IL-4, the major inducer of the Th2 phenotype, may explain the stability of the Th1 state.

scholarly journals Reversibility of T helper 1 and 2 populations is lost after long-term stimulation.

1996 ◽  
Vol 183 (3) ◽  
pp. 901-913 ◽  
Author(s):  
E Murphy ◽  
K Shibuya ◽  
N Hosken ◽  
P Openshaw ◽  
V Maino ◽  
...  
Keyword(s):  
Immune Response ◽  
Single Cells ◽  
Interleukin 4 ◽  
Th2 Cells ◽  
Th1 Cells ◽  
T Helper ◽  
T Helper 1 ◽  
Ifn Gamma ◽  
Th1 And Th2

Commitment of T helper 1 (Th1) or Th2 populations developing during an immune response to a pathogen, or an inappropriate immune response to an allergen or autoantigen, may determine the difference between health and chronic disease. We show that strongly polarized Th1 and Th2 populations assessed by immunoassay are heterogeneous using flow cytometry to detect single cells producing interferon gamma (IFN-gamma) and interleukin 4 (IL-4). Th1 populations arising after 1 wk of stimulation in IL-12 plus anti-IL-4 antibodies could convert to Th2 cells when restimulated in IL-4. Th2 populations resulting from stimulation for 1 wk in IL-4 could give rise to Th1 cells upon restimulation in IL-12 plus anti-IL-4. In contrast, the cytokine profiles of long-term Th1 and Th2 populations arising originally from repeated stimulation in IL-12 or IL-4 appeared more homogeneous and were not reversible, although IL-4 dramatically reduced the number of IFN-gamma-producing Th1 cells. This may explain previous reports that Th1 cells can be converted to Th2 cells.

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