scholarly journals Th17 Cells in Autoimmune and Infectious Diseases

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
José Francisco Zambrano-Zaragoza ◽  
Enrique Jhonatan Romo-Martínez ◽  
Ma. de Jesús Durán-Avelar ◽  
Noemí García-Magallanes ◽  
Norberto Vibanco-Pérez
Keyword(s):  
T Cell ◽  
Autoimmune Diseases ◽  
Th17 Cells ◽  
Strong Association ◽  
Cell Subset ◽  
Cd4 T Cell ◽  
Th2 Cells ◽  
Cell Mediated Immunity ◽  
Th Cell ◽  
Th1 And Th2

The view of CD4 T-cell-mediated immunity as a balance between distinct lineages of Th1 and Th2 cells has changed dramatically. Identification of the IL-17 family of cytokines and of the fact that IL-23 mediates the expansion of IL-17-producing T cells uncovered a new subset of Th cells designated Th17 cells, which have emerged as a third independent T-cell subset that may play an essential role in protection against certain extracellular pathogens. Moreover, Th17 cells have been extensively analyzed because of their strong association with inflammatory disorders and autoimmune diseases. Also, they appear to be critical for controlling these disorders. Similar to Th1 and Th2 cells, Th17 cells require specific cytokines and transcription factors for their differentiation. Th17 cells have been characterized as one of the major pathogenic Th cell populations underlying the development of many autoimmune diseases, and they are enhanced and stabilized by IL-23. The characteristics of Th17 cells, cytokines, and their sources, as well as their role in infectious and autoimmune diseases, are discussed in this review.

scholarly journals The Cxxc1 subunit of the Trithorax complex directs epigenetic licensing of CD4+ T cell differentiation

2021 ◽  
Vol 218 (4) ◽  
Author(s):  
Masahiro Kiuchi ◽  
Atsushi Onodera ◽  
Kota Kokubo ◽  
Tomomi Ichikawa ◽  
Yuki Morimoto ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
Allergic Airway Inflammation ◽  
T Cell Differentiation ◽  
Cd4 T Cell ◽  
Th2 Cells ◽  
Th2 Differentiation ◽  
Later Phase ◽  
Th1 And Th2

Different dynamics of gene expression are observed during cell differentiation. In T cells, genes that are turned on early or turned off and stay off have been thoroughly studied. However, genes that are initially turned off but then turned on again after stimulation has ceased have not been defined; they are obviously important, especially in the context of acute versus chronic inflammation. Using the Th1/Th2 differentiation paradigm, we found that the Cxxc1 subunit of the Trithorax complex directs transcription of genes initially down-regulated by TCR stimulation but up-regulated again in a later phase. The late up-regulation of these genes was impaired either by prolonged TCR stimulation or Cxxc1 deficiency, which led to decreased expression of Trib3 and Klf2 in Th1 and Th2 cells, respectively. Loss of Cxxc1 resulted in enhanced pathogenicity in allergic airway inflammation in vivo. Thus, Cxxc1 plays essential roles in the establishment of a proper CD4+ T cell immune system via epigenetic control of a specific set of genes.

scholarly journals CD4+ T-Cell Plasticity in Non-Infectious Retinal Inflammatory Disease

2021 ◽  
Vol 22 (17) ◽  
pp. 9584
Author(s):  
Yi-Hsing Chen ◽  
Sue Lightman ◽  
Virginia L. Calder
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Th17 Cells ◽  
Cell Subset ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Dual Function ◽  
Interleukin 17 ◽  
Th1 Cells

Non-infectious uveitis (NIU) is a potentially sight-threatening disease. Effector CD4+ T cells, especially interferon-γ-(IFNγ) producing Th1 cells and interleukin-17-(IL-17) producing Th17 cells, are the major immunopathogenic cells, as demonstrated by adoptive transfer of disease in a model of experimental autoimmune uveitis (EAU). CD4+FoxP3+CD25+ regulatory T cells (Tregs) were known to suppress function of effector CD4+ T cells and contribute to resolution of disease. It has been recently reported that some CD4+ T-cell subsets demonstrate shared phenotypes with another CD4+ T-cell subset, offering the potential for dual function. For example, Th17/Th1 (co-expressing IFNγ and IL-17) cells and Th17/Treg (co-expressing IL-17 and FoxP3) cells have been identified in NIU and EAU. In this review, we have investigated the evidence as to whether these ‘plastic CD4+ T cells’ are functionally active in uveitis. We conclude that Th17/Th1 cells are generated locally, are resistant to the immunosuppressive effects of steroids, and contribute to early development of EAU. Th17/Treg cells produce IL-17, not IL-10, and act similar to Th17 cells. These cells were considered pathogenic in uveitis. Future studies are needed to better clarify their function, and in the future, these cell subsets may in need to be taken into consideration for designing treatment strategies for disease.

scholarly journals Differential Th Cell-Related Immune Responses in Young Physically Active Men after an Endurance Effort

2020 ◽  
Vol 9 (6) ◽  
pp. 1795
Author(s):  
Dorota Kostrzewa-Nowak ◽  
Robert Nowak
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Age Groups ◽  
Cell Subset ◽  
Treg Cells ◽  
T Cell Subsets ◽  
Th2 Cells ◽  
T Helper 17 ◽  
Physically Active ◽  
Th Cell

The participation of T cell subsets in the modulation of immunity in athletes triggered by maximal effort was investigated. In total, 80 physically active young men (range 16–20 years) were divided into 5 age groups: 16, 17, 18, 19, and 20 years old. They performed efficiency tests on mechanical treadmills until exhaustion. White blood cell (WBC) and lymphocyte (LYM) counts were determined, and the type 1 (Th1), type 2 (Th2) helper T cells, T helper 17 (Th17), and T regulatory (Treg) cell distribution and plasma levels of selected cytokines were analyzed. An increase in WBC and LYM counts after the test and in Th1 and Treg cells after the test and in recovery was observed. There were no changes in Th2 cells. An increase in interleukins (IL): IL-2 and IL-8 was observed. The IL-6 level was altered in all studied groups. IL-17A and interferon gamma (IFN-γ) levels were increased in all studied groups. The mechanism of differential T cell subset activation may be related to athletes’ age. The novel findings of this study are the involvement of Th17 cells in post-effort immune responses and the participation of IL-6 in post-effort and the long-term biological effect of endurance effort.

scholarly journals CTLA-4 Engagement Inhibits Th2 but not Th1 Cell Polarisation

2003 ◽  
Vol 10 (1) ◽  
pp. 13-17 ◽  
Author(s):  
Vanessa Ubaldi ◽  
Lucia Gatta ◽  
Luigia Pace ◽  
Gino Doria ◽  
Claudio Pioli
Keyword(s):  
Transcriptional Activation ◽  
Cell Subset ◽  
Th2 Cells ◽  
T Helper ◽  
Th1 Cell ◽  
Th Cell ◽  
Ifn Γ ◽  
Culture Supernatants ◽  
Th1 And Th2

CTLA-4 deficient mice show severe lymphoproliferative disorders with T helper sub-population skewed toward the Th2 phenotype. In the present work, we investigated the role of CTLA-4 in T helper cell subset differentiation. Naïve CD4+cells were stimulated with anti-CD3 and anti-CD28 mAbs in the presence of either IL-12 or IL-4 to induce polarisation to Th1 or Th2 cells, respectively. Under these two polarising conditions cells express comparable levels of CTLA-4. CTLA-4 was stimulated by plastic-bound mAb. The frequency of IFN-γ- and IL-4-producing cells were estimated by FACS analysis. In parallel cultures, polarised Th1 and Th2 cells were re-stimulated with anti-CD3 and anti-CD28 mAbs for 48 h and their culture supernatants analysed by ELISA. Results show that CTLA-4 engagement during differentiation inhibits polarisation of naïve CD4+cells to the Th2 but not the Th1 cell subset. At variance, once cells are polarised, CTLA-4 engagement inhibits cytokine production in both effector Th2 and Th1 cells. Altogether these data indicate that CTLA-4 may interfere not only in the signalling involved in acute transcriptional activation of both Th1 and Th2 cells but also in the development of one of the Th cell subsets.

scholarly journals Helper T cell differentiation enters a new era: Le Roi est mort; vive le Roi!

2006 ◽  
Vol 203 (4) ◽  
pp. 809-812 ◽  
Author(s):  
Cristina M. Tato ◽  
Arian Laurence ◽  
John J. O'Shea
Keyword(s):  
T Cell ◽  
Cell Biology ◽  
Cell Subset ◽  
Th2 Cells ◽  
T Helper ◽  
New Era ◽  
Th Cell ◽  
T Cell Biology ◽  
New Evidence ◽  
Th 1

In the dark ages of T cell biology, we considered two fates for differentiated CD4+ T cells: T helper (Th)1 and Th2 cells. Now we know that the reality is much more complex and interesting. The newest Th cell subset produces the cytokine IL-17. New evidence shows that the IL-17–related cytokine IL-25 is essential for Th2 responses in two infectious disease models.

scholarly journals Long-Term CD4 Th1 and Th2 Memory following Acute Lymphocytic Choriomeningitis Virus Infection

1998 ◽  
Vol 72 (10) ◽  
pp. 8281-8288 ◽  
Author(s):  
Jason K. Whitmire ◽  
Mary S. Asano ◽  
Kaja Murali-Krishna ◽  
M. Suresh ◽  
Rafi Ahmed
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Lymphocytic Choriomeningitis ◽  
Lymphocytic Choriomeningitis Virus ◽  
Cd4 T Cell ◽  
Th2 Cells ◽  
Th2 Responses ◽  
Th1 And Th2

ABSTRACT CD4 T cells play a central role in viral immunity. They provide help for B cells and CD8 T cells and can act as effectors themselves. Despite their importance, relatively little is known about the magnitude and duration of virus-specific CD4 T-cell responses. In particular, it is not known whether both CD4 Th1 memory and CD4 Th2 memory can be induced by viral infections. To address these issues, we quantitated virus-specific CD4 Th1 (interleukin 2 [IL-2] and gamma-interferon) and Th2 (IL-4) responses in mice acutely infected with lymphocytic choriomeningitis virus (LCMV). Using two sensitive assays (enzyme-linked immunospot assay and intracellular stain) to measure cytokine production at the single-cell level, we found that both CD4 Th1 and Th2 responses were induced during primary LCMV infection. At the peak (day 8) of the response, the frequency of LCMV-specific CD4 Th1 cells was 1/35 to 1/160 CD4 T cells, and the frequency of Th2 cells was 1/400. After viral clearance, the numbers of virus-specific CD4 T cells dropped to 1/260 to 1/3,700 and then were maintained at this level indefinitely. Upon rechallenge with LCMV, both CD4 Th1 and Th2 memory cells made an anamnestic response in vivo. These results show that unlike some microbial infections in which only Th1 or Th2 responses are seen, an acute viral infection can induce a mixed CD4 T-cell response with long-term memory.

scholarly journals Progressive loss of CD8+ T cell-mediated control of a gamma-herpesvirus in the absence of CD4+ T cells.

1996 ◽  
Vol 184 (3) ◽  
pp. 863-871 ◽  
Author(s):  
R D Cardin ◽  
J W Brooks ◽  
S R Sarawar ◽  
P C Doherty
Keyword(s):  
T Cells ◽  
T Cell ◽  
Respiratory Tract ◽  
Cd8 T Cells ◽  
Cell Subset ◽  
Cd8 T Cell ◽  
Cd4 T Cell ◽  
Productive Infection ◽  
Cell Mediated Immunity ◽  
Murine Gammaherpesvirus

A unique experimental model has been developed for dissecting the integrity of CD8+ T cell-mediated immunity to a persistent gammaherpesvirus under conditions of CD4+ T cell deficiency. Respiratory challenge of major histocompatibility complex class II -/- and +/+ C57BL/6J mice with the murine gammaherpesvirus 68 (MHV-68) leads to productive infection of both lung and adrenal epithelial cells. Virus titers peak within 5-10 d, and are no longer detected after day 15. Persistent, latent infection is established concurrently in splenic and lymph node B cells, with higher numbers of MHV-68+ lymphocytes being found in all lymphoid sites analyzed from the +/+ mice concurrent with the massive, but transient splenomegaly that occurred only in this group. From day 17, however, the numbers of infected B lymphocytes were consistently higher in the -/- group, while the frequency of this population diminished progressively in the +/+ controls. Infectious MHV-68 was again detected in the respiratory tract and the adrenals of the -/- (but not the +/+) mice from day 22 after infection. The titers in these sites rose progressively, with the majority of the -/- mice dying between days 120 and 133. Even so, some CD8+ effectors were still functioning as late as 100 d after infection. Depletion of CD8+ T cells at this stage led to higher virus titers in the -/- lung, and to the development of wasting in some of the -/- mice. Elimination of the CD8+ T cells from the +/+ group (day 80) increased the numbers of MHV-68+ cells in the spleen, but did not reactivate the infection in the respiratory tract. The results are consistent with the interpretation that CD8+ T cell-mediated control of this persistent gammaherpesvirus is progressively lost in the absence of the CD4+ T cell subset. This parallels what may be happening in AIDS patients who develop Kaposi's sarcoma and various Epstein Barr virus associated disease processes.

CD4 T Cell Subset Profiling in Biliary Atresia Reveals ICOS- Regulatory T Cells as a Favourable Prognostic Factor

2018 ◽  
Author(s):  
Shuhao Zhang ◽  
Shyamal Goswami ◽  
Jiaqiang Ma ◽  
Lu Meng ◽  
Youping Wang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Prognostic Factor ◽  
Regulatory T Cells ◽  
Biliary Atresia ◽  
Cell Subset ◽  
Cd4 T Cell ◽  
T Cell Subset

scholarly journals Rapid Development of Th2 Activity During T Cell Priming

2003 ◽  
Vol 10 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Adam F. Cunningham ◽  
Kai-Michael Toellner
Keyword(s):  
T Cells ◽  
T Cell ◽  
Rapid Development ◽  
Critical Role ◽  
Cell Polarization ◽  
Th2 Cells ◽  
Th1 Cells ◽  
T Helper ◽  
Th 1 ◽  
Th1 And Th2

The paradigm of T helper-1 (Th-1) and Th-2 cells developing from non-committed naïve precursors is firmly established. Th1 cells are characterized by IFN production and, in mice, the selective switching to IgG2a. Conversely IL-4 production and selective switching to IgG1 and IgE characterize Th2 cells. Analysis of Th2 inductionin vitroindicates that this polarization develops gradually in T cells activated by anti-CD3 in the presence of IL-4; conversely anti-CD3 and IFN induce Th1 cells. In this report, we explore evidence that indicates that the T helper cell polarizationin vivocannot solely be explained by the cytokine environment. This is provided by studying the early acquisition of Th1 and Th2 activities during responses to a mixture of Th1 and Th2-inducing antigens. It is shown that these divergent forms of T cell help can rapidly develop in cells within a single lymph node. It is argued that early polarization to show Th-1 or Th-2 behavior can be induced by signals delivered during cognate interaction between virgin T cells and dendritic cells, in the absence of type 1 or type 2 cytokines. This contrasts with the critical role of the cytokines in reinforcing the Th-phenotype and selectively expanding T helper clones.

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