The enhancer and promoter landscape of human regulatory and conventional T-cell subpopulations

Blood ◽  
2014 ◽  
Vol 123 (17) ◽  
pp. e68-e78 ◽  
Author(s):  
Christian Schmidl ◽  
Leo Hansmann ◽  
Timo Lassmann ◽  
Piotr J. Balwierz ◽  
Hideya Kawaji ◽  
...  
Keyword(s):  
T Cells ◽  
Transcription Factor ◽  
T Cell ◽  
Regulatory T Cells ◽  
Cell Type ◽  
Key Points ◽  
Cell Type Specific ◽  
Transcription Factor Networks ◽  
Cell Subpopulations ◽  
T Cell Subpopulations

Key Points Transcription and enhancer profiling reveal cell type–specific regulome architectures and transcription factor networks in conventional and regulatory T cells.

scholarly journals Regulatory T Cells in Melanoma Revisited by a Computational Clustering of FOXP3+ T Cell Subpopulations

2016 ◽  
Vol 196 (6) ◽  
pp. 2885-2892 ◽  
Author(s):  
Hiroko Fujii ◽  
Julie Josse ◽  
Miki Tanioka ◽  
Yoshiki Miyachi ◽  
François Husson ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Cell Subpopulations ◽  
T Cell Subpopulations

scholarly journals Interleukin-10 Improves Stroke Outcome by Controlling the Detrimental Interleukin-17A Response

2021 ◽  
Author(s):  
Marius Piepke ◽  
Bettina H. Clausen ◽  
Peter Ludewig ◽  
Jonas H. Vienhues ◽  
Tanja Bedke ◽  
...  
Keyword(s):  
T Cells ◽  
Ischemic Stroke ◽  
T Cell ◽  
Regulatory T Cells ◽  
Mouse Models ◽  
Γδ T Cells ◽  
Transgenic Mouse Models ◽  
Cell Subpopulations ◽  
T Cell Subpopulations ◽  
Deficient Mice

Abstract Background: Lymphocytes have dichotomous functions in ischemic stroke. Regulatory T cells are protective, while IL-17A from innate lymphocytes promotes the infarcts growth. With recent advances of T cell-subtype specific transgenic mouse models it now has become possible to study the complex interplay of T cell subpopulations in ischemic stroke.Methods: In a murine model of experimental stroke we analyzed the effects of IL-10 on the functional outcome for up to 14 days post-ischemia and defined the source of IL-10 in ischemic brains based on immunohistochemistry, flow cytometry, and bone marrow chimeric mice. We used neutralizing IL-17A antibodies, intrathecal IL-10 injections, and transgenic mouse models which harbor a deletion of the IL-10R on distinct T cell subpopulations to further explore the interplay between IL-10 and IL-17A pathways in the ischemic brain. Results: We demonstrate that IL-10 deficient mice exhibit significantly increased infarct sizes on days three and seven and enlarged brain atrophy and impaired neurological outcome on day fourteen following tMCAO. In ischemic brains IL-10 producing immune cells included regulatory T cells, macrophages, and microglia. Neutralization of IL-17A following stroke reversed the worse outcome in IL-10 deficient mice and intracerebral treatment with recombinant IL-10 revealed that IL-10 controlled IL-17A positive lymphocytes in ischemic brains. Importantly, IL-10 acted differentially on αβ and γδ T cells. IL-17A producing CD4+ αβ T cells were directly controlled via their IL-10-receptor (IL-10R), whereas IL-10 by itself had no direct effect on the IL-17A production in γδ T cells. The control of the IL-17A production in γδ T cells depended on an intact IL10R signaling in regulatory T cells (Tregs). Conclusions: Taken together, our data indicate a key function of IL-10 in restricting the detrimental IL-17A-signaling in stroke and further supports that IL-17A is a therapeutic opportunity for stroke treatment.

scholarly journals Interleukin-10 improves stroke outcome by controlling the detrimental Interleukin-17A response

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Marius Piepke ◽  
Bettina H. Clausen ◽  
Peter Ludewig ◽  
Jonas H. Vienhues ◽  
Tanja Bedke ◽  
...  
Keyword(s):  
T Cells ◽  
Ischemic Stroke ◽  
T Cell ◽  
Regulatory T Cells ◽  
Mouse Models ◽  
Γδ T Cells ◽  
Transgenic Mouse Models ◽  
Cell Subpopulations ◽  
T Cell Subpopulations ◽  
Deficient Mice

Abstract Background Lymphocytes have dichotomous functions in ischemic stroke. Regulatory T cells are protective, while IL-17A from innate lymphocytes promotes the infarct growth. With recent advances of T cell-subtype specific transgenic mouse models it now has become possible to study the complex interplay of T cell subpopulations in ischemic stroke. Methods In a murine model of experimental stroke we analyzed the effects of IL-10 on the functional outcome for up to 14 days post-ischemia and defined the source of IL-10 in ischemic brains based on immunohistochemistry, flow cytometry, and bone-marrow chimeric mice. We used neutralizing IL-17A antibodies, intrathecal IL-10 injections, and transgenic mouse models which harbor a deletion of the IL-10R on distinct T cell subpopulations to further explore the interplay between IL-10 and IL-17A pathways in the ischemic brain. Results We demonstrate that IL-10 deficient mice exhibit significantly increased infarct sizes on days 3 and 7 and enlarged brain atrophy and impaired neurological outcome on day 14 following tMCAO. In ischemic brains IL-10 producing immune cells included regulatory T cells, macrophages, and microglia. Neutralization of IL-17A following stroke reversed the worse outcome in IL-10 deficient mice and intracerebral treatment with recombinant IL-10 revealed that IL-10 controlled IL-17A positive lymphocytes in ischemic brains. Importantly, IL-10 acted differentially on αβ and γδ T cells. IL-17A producing CD4+ αβ T cells were directly controlled via their IL-10-receptor (IL-10R), whereas IL-10 by itself had no direct effect on the IL-17A production in γδ T cells. The control of the IL-17A production in γδ T cells depended on an intact IL10R signaling in regulatory T cells (Tregs). Conclusions Taken together, our data indicate a key function of IL-10 in restricting the detrimental IL-17A-signaling in stroke and further supports that IL-17A is a therapeutic opportunity for stroke treatment.

scholarly journals Adult Renal Stem/Progenitor Cells Can Modulate T Regulatory Cells and Double Negative T Cells

2020 ◽  
Vol 22 (1) ◽  
pp. 274
Author(s):  
Claudia Curci ◽  
Angela Picerno ◽  
Nada Chaoul ◽  
Alessandra Stasi ◽  
Giuseppe De Palma ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Progenitor Cells ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Double Negative ◽  
Chronic Injury ◽  
Peripheral Blood Mononuclear ◽  
Cell Subpopulations ◽  
T Cell Subpopulations

Adult Renal Stem/Progenitor Cells (ARPCs) have been recently identified in the human kidney and several studies show their active role in kidney repair processes during acute or chronic injury. However, little is known about their immunomodulatory properties and their capacity to regulate specific T cell subpopulations. We co-cultured ARPCs activated by triggering Toll-Like Receptor 2 (TLR2) with human peripheral blood mononuclear cells for 5 days and 15 days and studied their immunomodulatory capacity on T cell subpopulations. We found that activated-ARPCs were able to decrease T cell proliferation but did not affect CD8+ and CD4+ T cells. Instead, Tregs and CD3+ CD4- CD8- double-negative (DN) T cells decreased after 5 days and increased after 15 days of co-culture. In addition, we found that PAI1, MCP1, GM-CSF, and CXCL1 were significantly expressed by TLR2-activated ARPCs alone and were up-regulated in T cells co-cultured with activated ARPCs. The exogenous cocktail of cytokines was able to reproduce the immunomodulatory effects of the co-culture with activated ARPCs. These data showed that ARPCs can regulate immune response by inducing Tregs and DN T cells cell modulation, which are involved in the balance between immune tolerance and autoimmunity.

scholarly journals Disproportion in T-cell subpopulations in immunodeficient mutant hr/hr mice.

1979 ◽  
Vol 149 (1) ◽  
pp. 228-233 ◽  
Author(s):  
A B Reske-Kunz ◽  
M P Scheid ◽  
E A Boyse
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Lymph Nodes ◽  
Salient Feature ◽  
Mutant Gene ◽  
Cell Subpopulations ◽  
T Cell Subpopulations

Mice of the HRS strain, which carry the mutant gene hr, were examined for abnormalities in representation of the three T-cell sets Ly1, Ly23, and Ly123 in the spleen. The salient feature of hr/hr mice, which are immunologically deficient, in comparison with +/hr segregants, was a gross disproportion in numbers of cells belonging to the Ly1 and Ly123 sets, at the age of 3--3.5 mo. At this age, Ly123 cells of hr/hr spleen outnumbered Ly1 cells by 2:1, whereas in +/hr spleens Ly123 cells were outnumbered by approximately 1:2. Cells from pooled lymph nodes of hr/hr mice did not show a correspondingly gross disporprotion of Ly1 and Ly123 cells. Total counts of splenic T cells, and of B cells, were not significantly different in hr/hr and +/hr mice.

scholarly journals Autologous stem cell transplantation aids autoimmune patients by functional renewal and TCR diversification of regulatory T cells

Blood ◽  
2016 ◽  
Vol 127 (1) ◽  
pp. 91-101 ◽  
Author(s):  
Eveline M. Delemarre ◽  
Theo van den Broek ◽  
Gerdien Mijnheer ◽  
Jenny Meerding ◽  
Ellen J. Wehrens ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Regulatory T Cells ◽  
Stem Cell Transplantation ◽  
Clinical Improvement ◽  
Autologous Stem Cell Transplantation ◽  
T Cell Reconstitution ◽  
Key Points ◽  
Autologous Hsct

Key Points Autologous HSCT induces functional renewal of regulatory T cells as well as a strong Treg TCR diversification in autoimmune patients. Adding regulatory T cells to the graft does not lead to additional clinical improvement but results in delayed donor T-cell reconstitution.

scholarly journals Selective expression of H-2 (i-region) loci controlling determinants on helper and suppressor T lymphocytes.

1976 ◽  
Vol 144 (3) ◽  
pp. 685-698 ◽  
Author(s):  
K Okumura ◽  
L A Herzenberg ◽  
D B Murphy ◽  
H O McDevitt ◽  
L A Herzenberg
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Lymphoid Cells ◽  
Control Surface ◽  
Cell Subpopulation ◽  
Selective Expression ◽  
Suppressor T Lymphocytes ◽  
Cell Subpopulations ◽  
T Cell Subpopulations

Data presented here show that locidentify in the I-region of the H-2 gene complex are selectively expressed in different functional T-cell subpopulations. These loci are closely linked (or possibly identical) to loci that control immune responses. They control surface determinants which identify helper and suppressor T lymphocytes. Determinants described here on allotype suppressor T cells (Ts) are found on normal (nonsuppressed) lymphoid cells, but are not found on helper T cells (Th). These determinants are controlled by a locus mapping in the I region of the H-2 complex. In an accompanying publication we show that this locus (Ia-4) marks a new I subregion (I-J) and is expressed only on T cells. Thus Ia-4 determinants idenfity a T-cell subpopulation which includes Ts but not Th. Th also carry identifying surface determinants controlled by loci that map to the H-2 complex, probably within the I region. These determinants are not found on Ts. Data presented also establish that loci in the I region control determinants on Th, but do not conclusively demonstrate that these are the determinants that distinguish Th from Ts. The selective expression of H-2-controlled determinants on Ts and Th suggests that these determinants are directly involved in immunoregulation.

FoxP3, a Key Molecule in CD4+CD25+ Regulatory T Cells, Express in Adult T Cell Leukemia/Lymphoma Cells and Relates to Clinicopathological Features.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3255-3255
Author(s):  
Kennosuke Karube ◽  
Koichi Ohshima ◽  
Junji Suzumiya ◽  
Mine Harada ◽  
Masahiro Kikuchi
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Opportunistic Infection ◽  
Large Cell ◽  
Cell Leukemia ◽  
Cell Type ◽  
Lymphoma Cells ◽  
Adult T Cell Leukemia ◽  
Pleomorphic Cell

Abstract AIMES: Adult T cell leukemia/lymphoma (ATLL) is an aggressive neoplastic disease and opportunistic infections often occur in patients with ATLL. However, the underlying mechanisms of such infections remain unknown. Recently, regulatory T cells (Treg), characterized by coexpression of CD4 and CD25, are proposed as a new T cell group with definite function. Treg suppresses normal T cells proliferation in vitro and play an important role to suppress autoimmune disease in vivo. But the deregulated proliferation such immunosuppressive T cells may induce immunodeficient status. We analyzed the expression of forkhead/winged helix transcription factor (FoxP3), known to be important for the function and specific marker of Treg cells, on ATLL cells. METHODS and RESULTS: FoxP3 expression was detected in both peripheral blood and lymph nodes in part of ATLL cases by real-time PCR and immunostaining (Figure). Next, we immunostained lymph node sections from 112 cases and 36 cases showed positivity for FoXP3. Morphologically, 112 ATLL cases were divided into three variants, namely pleomorphic cell type (61 cases), large cell type (45 cases), and anaplastic large cell type (16 cases). FoxP3 was expressed (more than 30% of the lymphoma cells) in a proportion of pleomorphic cell type (24 cases, 39.4%) and large cell type (12 cases, 26.7%) but no cases of anaplastic type showed positivity. Especially, strong expression (more than 50% of the lymphoma cells) was observed in 15 cases and 12 cases were pleomorphic cell type (Table). A proportion of FoxP3 positive ATLL cases showed intermingled EBV-infected transformed lymphocytes, suggesting local immunodeficient condition (Very few FoxP3 negative cases showed EBV-infected lymphocytes)(Table). Clinically, more proportion of FoxP3 positive ATLL cases showed opportunistic infection, for example Pneumocystis Carinii infections, Herpes zoster virus infection, antibiotics-refractory abscesses (Table). CONCLUSION: A proliferation of FoxP3 positive lymphoma cells may contribute to the tumor invasion and opportunistic infection by inducing local and diffuse immunodeficient status respectively. Figure Figure

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