A New Role for Conivaptan in Ulcerative Colitis in Mice: Inhibiting Differentiation of CD4+T Cells into Th1 Cells

2021 ◽  
Author(s):  
Dandan Dou ◽  
Yuge Ji ◽  
Junjie Zheng ◽  
Jingxin Li ◽  
Xiaolong Zhu ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
T Cells ◽  
Cd4 T Cells ◽  
Th1 Cells

scholarly journals SERPINB10 contributes to asthma by inhibiting the apoptosis of allergenic Th2 cells

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yuqing Mo ◽  
Ling Ye ◽  
Hui Cai ◽  
Guiping Zhu ◽  
Jian Wang ◽  
...  
Keyword(s):  
T Cells ◽  
Allergic Asthma ◽  
Cd4 T Cells ◽  
Quantitative Polymerase Chain Reaction ◽  
Allergic Inflammation ◽  
Specific Ige ◽  
Th2 Cells ◽  
Th1 Cells ◽  
Th2 Response ◽  
Th1 And Th2

Abstract Background Serine peptidase inhibitor, clade B, member 10 (SERPINB10) contributes to allergic inflammation in asthma. However, its role in the T-helper type 2 (Th2) response of allergic asthma is not known. The goal of this study was to unveil the function of SERPINB10 in the Th2 response of allergic asthma and the mechanism by which SERPINB10 affects the viability of Th2 cells. Methods Th2 cytokines and serum levels of house dust mite (HDM)-specific IgE in bronchoalveolar lavage fluid were examined by ELISA in an HDM-induced asthma model. The number and apoptosis of Th1 and Th2 cells in mouse lungs were measured by flow cytometry. Naïve CD4 T cells from patients with asthma were cultured under appropriate polarizing conditions to generate Th1 and Th2 cells. SERPINB10 expression in polarized Th1 and Th2 cells was quantified by real-time reverse transcription-quantitative polymerase chain reaction. SERPINB10 expression was knocked down in human CD4 T cells with lentivirus. Results Knockdown of SERPINB10 expression significantly diminished HDM-induced Th2 cytokine secretion and level of HDM-specific IgE. After HDM exposure, SERPINB10-knockdown mice had diminished numbers of Th2 cells, but similar numbers of Th1 cells, compared with those in negative-control mice. Th2 cells of SERPINB10-knockdown mice were more susceptible to apoptosis than that of control mice. Stimulating T-cell receptors (TCRs) with anti-CD3 antibody caused upregulation of SERPINB10 expression in polarized Th2 cells, but not polarized Th1 cells. Knockdown of SERPINB10 expression resulted in fewer numbers and greater apoptosis of polarized Th2 cells. Conclusion Our results suggest that SERPINB10 may contribute to allergic inflammation and the Th2 response of asthma by inhibiting the apoptosis of Th2 cells.

scholarly journals Aggregatibacter actinomycetemcomitans GroEL Protein Promotes Conversion of Human CD4+ T Cells into IFNγ IL10 Producing Tbet+ Th1 Cells

PLoS ONE ◽  
2012 ◽  
Vol 7 (11) ◽  
pp. e49252 ◽  
Author(s):  
Tahsin Saygılı ◽  
Semih Can Akıncılar ◽  
Bünyamin Akgül ◽  
Ayten Nalbant
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Aggregatibacter Actinomycetemcomitans ◽  
Th1 Cells ◽  
Groel Protein

T1212 Upregulation of E3 Ubiquitin Ligases Related to T Cell Anergy in CD4+ T Cells Isolated from Patients with Ulcerative Colitis in Remission

2008 ◽  
Vol 134 (4) ◽  
pp. A-508
Author(s):  
Satoshi Egawa ◽  
Hideki Iijima ◽  
Shinichiro Shinzaki ◽  
Sachiko Nakajima ◽  
Jumpei Kondo ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Ubiquitin Ligases ◽  
E3 Ubiquitin Ligases ◽  
T Cell Anergy ◽  
Cell Anergy

scholarly journals LRCH1 suppresses migration of CD4+ T cells and refers to disease activity in ulcerative colitis

2020 ◽  
Vol 17 (5) ◽  
pp. 599-608 ◽  
Author(s):  
Yibo Wang ◽  
Hairong Zhang ◽  
Heng He ◽  
Kuankuan Ai ◽  
Wei Yu ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
T Cells ◽  
Disease Activity ◽  
Cd4 T Cells

scholarly journals Regulatory interactions between CD45RBhigh and CD45RBlow CD4+ T cells are important for the balance between protective and pathogenic cell-mediated immunity.

1994 ◽  
Vol 179 (2) ◽  
pp. 589-600 ◽  
Author(s):  
F Powrie ◽  
R Correa-Oliveira ◽  
S Mauze ◽  
R L Coffman
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Scid Mice ◽  
Th2 Cells ◽  
Cell Mediated Immunity ◽  
Th1 Cells ◽  
Ifn Gamma ◽  
Th1 Response ◽  
Major Infection

BALB/c mice infected with the intracellular protozoan Leishmania major mount a T helper cell 2 (Th2) response that fails to control growth of the parasite and results in the development of visceral leishmaniasis. Separation of CD4+ T cells into CD45RBhigh and CD45RBlow subsets showed that the L. major-specific Th2 cells were contained within the CD45RBlow population as these cells produced high levels of antigen-specific interleukin 4 (IL-4) in vitro and transferred a nonhealing response to L. major-infected C.B-17 scid mice. In contrast, the CD45RBhighCD4+ population contained L. major-reactive cells that produced interferon gamma (IFN-gamma) in vitro and transferred a healing Th1 response to L. major-infected C.B-17 scid mice. Transfer of the Th1 response by the CD45RBhigh population was inhibited by the CD45RBlow population by a mechanism that was dependent on IL-4. These data indicate that L. major-specific Th1 cells do develop in BALB/c mice, but their functional expression is actively inhibited by production of IL-4 by Th2 cells. In this response, the suppressed Th1 cells can be phenotypically distinguished from the suppressive Th2 cells by the level of expression of CD45RB. Although the CD45RBhigh population mediated a protective response to L. major, C.B-17 scid mice restored with this population developed a severe inflammatory response in the colon that was independent of L. major infection, and was prevented by cotransfer of the CD45RBlow population. The colitis appeared to be due to a dysregulated Th1 response as anti-IFN-gamma, but not anti-IL-4, prevented it. Taken together, the data show that the CD4+ T cell population identified by high level expression of the CD45RB antigen contains cells that mediate both protective and pathogenic Th1 responses and that the reciprocal CD45RBlow population can suppress both of these responses. Whether suppression of cell-mediated immunity is beneficial or not depends on the nature of the stimulus, being deleterious during L. major infection but crucial for control of potentially pathogenic inflammatory responses developing in the gut.

T-Rapa Cell Clinical Products Contain a Balance of Minimally Differentiated Th2/Th1 Effector Cells Depleted of Treg Cells

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 352-352 ◽  
Author(s):  
Miriam E. Mossoba ◽  
Jacopo Mariotti ◽  
Xiao-Yi Yan ◽  
Anu Gangopadhyay ◽  
Mathew Winterton ◽  
...  
Keyword(s):  
T Cells ◽  
Transcription Factor ◽  
Cd4 T Cells ◽  
Treg Cells ◽  
Cytokine Secretion ◽  
Th2 Cells ◽  
Th1 Cells ◽  
Cell Secretion ◽  
Th2 Cytokine ◽  
Low Levels

Abstract Abstract 352 Ex-vivo expansion of murine donor CD4+ T cells using co-stimulation, IL-4, and rapamycin generated a T cell population (T-rapa cells) that beneficially modulated GVHD, graft rejection, and GVT effects. We thus conducted a clinical trial to evaluate T-rapa cell infusion after HLA-matched sibling allogeneic HCT. In one trial arm, T-rapa cell infusion (2.5 × 107 cells/kg; d 14 post-HCT) safely accelerated alloengraftment after low-intensity host conditioning, as evidenced by: conversion of mixed chimerism to predominant donor chimerism in the majority of patients by d 100 post-HCT and a low rate of grade II to IV acute GVHD (10%; 4/40 cases). This abstract characterizes the T-rapa clinical products (n=48), particularly with respect to the balance of Th1, Th2, and Treg cells and the magnitude of effector function (cytokine secretion); this latter aspect is relevant because in animal models, T cells of limited differentiation mediate increased in vivo effects upon adoptive transfer. Transplant donors underwent steady-state leukapheresis. CD4+ T cells were then purified (Miltenyi.. CliniMACS) and expanded in Lifecell.. bags for 12 days using co-stimulation (anti-CD3, anti-CD28 coated magnetic beads) and media containing rhIL-2, rhIL-4, and rapamycin. T-rapa products contained minimal cells of naive phenotype (CD45RA+ cells: 2 ± 0.4%) and were comprised of both central memory cells (CCR7+: 28 ± 2%) and effector memory cells (CCR7−: 67 ± 2%). Phenotyping assays were performed on T-rapa clinical products at d 12 of culture (time of cell product infusion); in addition, to assess phenotype stability, assays were performed after an additional 6 days of culture after co-stimulation without IL-4 and rapamycin (“day 18”). For comparison, four separate CD4+ T cell culture conditions were established from each of n=8 normal donors. For these control cultures, CD4+ T cells were co-stimulated and propagated for 12 days in tissue culture flasks using: (1) IL-2, IL-4 (“Th2”); (2) IL-2, IL-4 plus rapamycin (“T-rapa”); (3) IL-2, IFN-a (“Th1”); and (4) IL-2, IFN-a plus rapamycin (“Th1-rapa”). Phenotyping results are shown in Fig. 1. In the four flask cultures, there was modest skewing of the Th2/Th1 balance, as indicated by relatively comparable expression of the Th2 transcription factor GATA-3 and the Th1 transcription factor T-bet by intra-cellular flow cytometry (Fig. 1A). In marked contrast, day 12 T-rapa clinical products expressed a highly polarized Th2/Th1 balance (GATA-3/T-bet ratio of 28 ± 9 [mean ± SEM]); this Th2/Th1 balance was relatively stable after additional culture without IL-4 and rapamycin (“Day 18”). The median frequency of transcription factor expression was 11.5% for GATA-3 (range: 3–37%), 5.1% for T-bet (range: 0–18%), and < 1% expression of the Treg transcription factor FoxP3 (range: 0–0.7%). T-rapa clinical products were evaluated for cytokine secretion in response to co-stimulation at day 12 and day 18 of culture; supernatants were tested for Th2 cytokines (Fig. 1B) and Th1/Th17 cytokines (Fig. 1C). Day 12 T-rapa clinical products secreted each Th2 cytokine measured. The magnitude (pg/ml) of T-rapa cell Th2 cytokine secretion was approximately 2-log reduced relative to control Th2 cells; day 18 T-rapa cell secretion of Th2 cytokines was increased relative to day 12 values, but still reduced relative to control Th2 cells. Day 12 T-rapa clinical products did not secrete IL-17 and secreted low levels of IFN-g, IL-2, and TNF-a (1-3 log reduced relative to Th1 control cells). Day 18 T-rapa cell secretion of IFN-g and TNF-a was increased relative to day 12 values, but still reduced relative to control Th1 cells. Remarkably, day 18 T-rapa cell secretion of IL-2 was greatly diminished relative to day 12 values, and IL-17 secretion remained at minimal levels. In conclusion, T-rapa cell clinical products are comprised of a balance of Th2 and Th1 effector CD4+ T cells, with minimal contamination from Treg or Th17 cells. The T-rapa cell clinical products possessed limited differentiation plasticity and secreted low levels of Th2 and Th1 cytokines. Adoptive transfer of a balance of minimally differentiated and fixed polarity donor Th2/Th1 cells represents a novel approach to safely accelerate alloengraftment after low-intensity conditioning. Disclosures: No relevant conflicts of interest to declare.

Functional Characterization of CD4+ T-Cells in Aplastic Anemia (AA)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1340-1340 ◽  
Author(s):  
Shahram Y Kordasti ◽  
Judith C. W. Marsh ◽  
Sufyan Al-Khan ◽  
Jie Jiang ◽  
Alexander E Smith ◽  
...  
Keyword(s):  
T Cells ◽  
Treatment Group ◽  
High Throughput ◽  
Cd4 T Cells ◽  
Th17 Cells ◽  
Absolute Number ◽  
Th2 Cells ◽  
Th1 Cells ◽  
Ifn Γ ◽  
Pre Treatment

Abstract Abstract 1340 We have examined the role of CD4+ T-cells in the pathogenesis of AA in 63 patients, 48 of whom were analyzed at diagnosis and 15 following immunosuppressive therapy (IST). Absolute numbers of CD4+ regulatory T cells (Tregs, defined as CD3+CD4+CD25highCD27+Foxp3+) were lower in pre-treatment AA patients compared to 10 healthy donors (HDs) (5.5 × 106 v 1.4 × 107)(p=0.01). In patients with severe (SAA) and very severe AA (VSAA), the absolute number and frequency of Tregs were lower than non-severe AA (NSAA) (4.4 × 106/L v 1 × 107/L)(p=0.01) and HDs (4.4 × 106/L v 3 × 107/L) (p<0.001). Absolute numbers of Th1 and Th2 cells in all pre-treatment patients were higher compared to HDs (6.4 × 107/L v 1.8 × 107/L)(p=0.03) for Th1 and (2.6 × 107/L v 2.4 × 106/L)(p=0.006) Th2 cells. Although mean percentages of AA Th17 cells were higher than in HDs (1.5% v 0.15%)(p=0.04), differences in absolute numbers were not significant. Absolute numbers of Th2 and Th17 cells were increased in SAA (1.3 × 107/L v 7.4 × 106/L for Th2)(p=0.01) compared to NSAA (5.7 × 106/L v 2.15 × 106/L for Th17)(p=0.02). Ratios of Th1/Tregs (p=0.003), Th2/Tregs (p=0.02), and Th17/Tregs (p=0.001) were higher in SAA and VSAA compared to NSAA. Percentage of both activated (CD4+CD45RA−CD25highFoxp3high) and resting (CD4+CD45RA+ CD25highFoxp3low) Tregs was decreased in AA patients, compared to HDs (p=0.004 and p=0.01), whereas cytokine secreting Tregs (CD4+CD45RA−CD25high Foxp3low) were increased in AA (p<0.003). Sorted Tregs from AA patients did not suppress cytokine secretion by autologous or HD T effectors (Te) cells in 1:1 co-cultures, whereas IL-2 and IFN-γ secretion by AA Te (CD4+CD25lowCD127high) was suppressible by allogeneic Tregs from HDs, confirming Tregs dysfunction. AA Tregs did not inhibit either CD154 or CD69 expression on Te cells. Tregs from AA patients secreted significantly more IFN-γ, TNF-α and IL-17 (p=0.02, p=0.02 and p=0.01, respectively) after 4 hours stimulation with PMA/Ionomycine compared to HDs. Expression levels of FoxP3, ROR□c and T-bet in AA Tregs was normal. IFN-γ secreting cells (Th1) were enriched using enrichment kit then further enriched by FACS sorting. CDR3 region products of TCR Vβ-chain were amplified using Vβ specific forward and Cβ reverse primers. CDR3 PCR products from AA patients and HDs were subjected 454 sequencing (Roche GS FLX titanium). Sequencing was performed to yield an average ‘depth’ in excess of 1000 clonally reads (1000x) for each sample specific CDR3 PCR amp icon. Reads were processed using Roche Amp icon Variant Analyzer software (AVA). Diversity of TCR receptors (measured by spectratyping and confirmed by high throughput deep sequencing) in AA Th1 cells was lower than HDs (p=0.037), as shown by the percentage and number of consensus clusters in total sequence reads. Interestingly, percentages of the most dominant CDR3 clones, revealed by high throughput sequencing, were higher in AA compared to HDs, regardless of spectratyping pattern. Global gene expression of Tregs was compared in 3 pre-IST AA patients and 5 HDs. A unique gene signature consisting of 86 genes that were significant was identified. There were 8 down regulated genes (fold change) in the pre-treatment group; PIN4 (−4.1), OR2T12 (−3.3), AMAC1 (−2.73), PERP (−2.69), UTS2 (−2.27), RNF139 (−2.13), COMMD9 (−2.09) and LOC100128356 (−2.01). The top 10 of 78 up-regulated genes in the pre-treatment group were HBB (19.5), PSME2 (13.8), CSDA (13.07), FAM127A (7.78), EXOSC1 (7.73), BPGM (7.43), CYSLTR1 (7.17), CHPT1 (6.96) and PLAC8 (6.71). qPCR analysis for CSDA, HBB, PSMiE2, PERP, PIN4, and UTS2 confirmed a similar trend to the microarray results. Interestingly absolute number of Tregs, and Th2/Treg ratio were higher in 10 IST responsive patients compared to 5 non-responsive patients (p=0.005 and 0.02, respectively). We show that expansion of Th1, Th2, Th17, and decreased/skewed Tregs immunophenotype and function are a consistent and defining feature of SAA and VSAA. Clonal expansion of Th1 cells is likely to be antigen driven and the presence of dysfunctional Tregs aggravates this autoimmune response. Increases of Tregs, and Th2/Treg ratios following IST predicts a favourable response to this treatment. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Induction of Interleukin 10–Producing, Nonproliferating Cd4+ T Cells with Regulatory Properties by Repetitive Stimulation with Allogeneic Immature Human Dendritic Cells

2000 ◽  
Vol 192 (9) ◽  
pp. 1213-1222 ◽  
Author(s):  
Helmut Jonuleit ◽  
Edgar Schmitt ◽  
Gerold Schuler ◽  
Jürgen Knop ◽  
Alexander H. Enk
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Mononuclear Cells ◽  
Repetitive Stimulation ◽  
Negative Regulator ◽  
Th1 Cells ◽  
Alloreactive T Cells ◽  
Stimulation Of

The functional properties of dendritic cells (DCs) are strictly dependent on their maturational state. To analyze the influence of the maturational state of DCs on priming and differentiation of T cells, immature CD83− and mature CD83+ human DCs were used for stimulation of naive, allogeneic CD4+ T cells. Repetitive stimulation with mature DCs resulted in a strong expansion of alloreactive T cells and the exclusive development of T helper type 1 (Th1) cells. In contrast, after repetitive stimulation with immature DCs the alloreactive T cells showed an irreversibly inhibited proliferation that could not be restored by restimulation with mature DCs or peripheral blood mononuclear cells, or by the addition of interleukin (IL)-2. Only stimulation of T cells with mature DCs resulted in an upregulation of CD154, CD69, and CD70, whereas T cells activated with immature DCs showed an early upregulation of the negative regulator cytotoxic T lymphocyte–associated molecule 4 (CTLA-4). These T cells lost their ability to produce interferon γ, IL-2, or IL-4 after several stimulations with immature DCs and differentiated into nonproliferating, IL-10–producing T cells. Furthermore, in coculture experiments these T cells inhibited the antigen-driven proliferation of Th1 cells in a contact- and dose-dependent, but antigen-nonspecific manner. These data show that immature and mature DCs induce different types of T cell responses: inflammatory Th1 cells are induced by mature DCs, and IL-10–producing T cell regulatory 1–like cells by immature DCs.

scholarly journals Infusion of Ex Vivo Activated Donor Type 2 Innate Lymphoid Cells Inhibit Th1 Activity and Reduces Acute Graft-Versus-Host Disease

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 538-538
Author(s):  
Danny Bruce ◽  
Michelle West ◽  
Trisha A Dant ◽  
Angela Panoskaltsis-Mortari ◽  
Bruce R. Blazar ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Cytokine Production ◽  
Lymphoid Cells ◽  
Th1 Cells ◽  
Gi Tract ◽  
Donor T Cells ◽  
Conditioning Therapy ◽  
Ifn Γ

Abstract The particular subsets of T cells that mediates aGvHD is not clear. Several studies have implicated Th1 and/or Th17 T cells in the pathogenesis of aGvHD. Pre-clinical data suggest that IFN-γ producing Th1 cells are perhaps more important for GI tract aGvHD whereas IL-17 producing Th17 cells are more important for skin and lung pathology. However, both murine models and clinical data indicate that suppression of Th1 and Th17 responses by shifting to a Th2 T cell phenotype limits aGvHD. One potential mechanism for the enhanced Th1 tropism of the lower GI tract is the role of conditioning therapy on the release of cytokines and bacterial products that may polarize naïve T cells toward Th1 cells. The explosion of data surrounding innate immune cells, such as type 2 innate lymphoid cells (ILC2) has increased the possibility of discovering additional candidate suppressive cells. In patients undergoing allo-HCT, peripheral blood ILCs slowly recover and activated ILCs are associated with reduced GVHD lethality. Since ILC2 cells may drive donor Th2 responses that reduce GVHD lethality and hence their deficiency may predispose to Th1 mediated GVHD, we quantified ILC2 numbers in the GI tract and secondary lymphoid organs after radiation. B6D2 mice were given a lethal dose of radiation and ILCs enumerated using flow cytometry. As shown by others, ILC3 cells in the lamina propria (LP) of the colon are resistant to radiation but CD4+ T cells in the LP, spleen and MLN are sensitive to radiation showing significant reduction of total cells within 24 hrs. In striking contrast to ILC3 cells, ILC2 cells from the LP of the colon and spleen were highly sensitivite to radiation. Thus, the absence of recipient ILC2 cells in the colon and MLN, may critically lead to alterations in the microenvironment leading to Th1 polarization in the lower GI tract induced after allo-SCT. Given ILC2 production of Th2 cytokines and the data indicating that shifting the cytokine micro-environment away from Th1/Th17 to Th2 reduces the severity of aGVHD, we hypothesized that co-transplantation of ILC2 cells would reduce aGvHD and increase survival after allo-SCT. ILC2 cells can be indentified as lin- and ICOS+, CD127+ and ST2+. ILC2 cells were expanded for 6 days in the presence of IL-7 and IL-33 which resulted in increased percentages of IL-4, IL-5 and IL-13 expressing cells with no evidence of expansion of other ILC groups based upon IFN-γ expression for ILC1 or IL-22 expression for ILC3 cells. To test the efficacy of restoring ILC2 cells after radiation, we performed survival studies in two distinct aGVHD models. In the B6 to BALB/c models of aGvHD after allo-SCT, co-transplantation of one dose of ILC2 cells significantly improved survival after allo-SCT (p<0.0001 log rank) (Figure 1A) with an increase in median survival of 12 days and a reduction in clinical GvHD score (Day 20 score, 6.5 ± 0.3 vs. 3.5 ± 0.4 SEM), beginning at day 10 in a very stringent MHC completely mismatched model. An even greater improvement in survival was seen with ILC2 infusion at the time of transplant in B6D2F1 recipients of B6 bone marrow and T cells. In the B6 to BALB/c model, analysis of donor T cells cytokine production by flow cytometry showed a significant reduction in the frequency of IFNγ producing CD4+ T cells in the LP of recipients of ILC2 cells (Figure 1B). Interestingly, we found that ILC2 cells were equally effective in the complete mismatch model when given on the day of transplant or seven days after transplant. In summary, we have shown that ILC2 cells are radiation sensitive and that co-infusion of a single dose of ILC2 can increase survival, reduce clinical signs of aGvHD and reduced Th1 cytokine production by donor T cells. These data suggest that the Th1 skewed microenvironment in target organs of GvHD seen after conditioning therapy may be due to reduce ILC2 numbers and replacing the ILC2 population with donor-derived cells in the transplant recipient returns the immune microenvironment to a more desirable, tolerogenic status. Figure 1 Figure 1. Donor ILC2 cells limit aGvHD. (A) Lethally irradiated BALB/c mice (850cGy) received 4.0 x 106 TCD BM (BM only), BM plus 5.0 x 105 total splenic T cells (Ctrl) or BM plus T cells with 2.0 x 106 ILC2 cells (Treatment). (A) Percent survival after allo-SCT. This represents 4 independent experiments combined, n=25. (B) Percentage of IFN-γ producing donor CD4+ T cells in the LP at day 12, represents 2 experiments, n=4 each. Disclosures No relevant conflicts of interest to declare.

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.

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