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 Distinct CD4−CD8− (Double-Negative) Memory T-Cell Subpopulations Are Associated With Indeterminate and Cardiac Clinical Forms of Chagas Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Livia Silva Araújo Passos ◽  
Carolina Cattoni Koh ◽  
Luísa Mourão Dias Magalhães ◽  
Maria do Carmo Pereira Nunes ◽  
Kenneth John Gollob ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chagas Disease ◽  
Central Memory ◽  
Effector Memory ◽  
Double Negative ◽  
Cytokine Network ◽  
Chagas Cardiomyopathy ◽  
Cell Subpopulations ◽  
T Cell Subpopulations

CD4−CD8− (double-negative, DN) T cells are critical orchestrators of the cytokine network associated with the pathogenic inflammatory response in one of the deadliest cardiomyopathies known, Chagas heart disease, which is caused by Trypanosoma cruzi infection. Here, studying the distribution, activation status, and cytokine expression of memory DN T-cell subpopulations in Chagas disease patients without cardiac involvement (indeterminate form—IND) or with Chagas cardiomyopathy (CARD), we report that while IND patients displayed a higher frequency of central memory, CARD had a high frequency of effector memory DN T cells. In addition, central memory DN T cells from IND displayed a balanced cytokine profile, characterized by the concomitant expression of IFN-γ and IL-10, which was not observed in effector memory DN T cells from CARD. Supporting potential clinical relevance, we found that the frequency of central memory DN T cells was associated with indicators of better ventricular function, while the frequency of effector memory DN T cells was not. Importantly, decreasing CD1d-mediated activation of DN T cells led to an increase in IL-10 expression by effector memory DN T cells from CARD, restoring a balanced profile similar to that observed in the protective central memory DN T cells. Targeting the activation of effector memory DN T cells may emerge as a strategy to control inflammation in Chagas cardiomyopathy and potentially in other inflammatory diseases where these cells play a key role.

scholarly journals Potent but transient immunosuppression of T-cells is a general feature of erythroid progenitor cells

2021 ◽  
Author(s):  
Tomasz M. Grzywa ◽  
Anna Sosnowska ◽  
Zuzanna Rydzynska ◽  
Michal Lazniewski ◽  
Dariusz Plewczynski ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Progenitor Cells ◽  
Mononuclear Cells ◽  
Early Stage ◽  
Erythroid Differentiation ◽  
Peripheral Blood Mononuclear ◽  
Erythroid Progenitor ◽  
Erythroid Progenitor Cells

AbstractErythroid progenitor cells (EPCs) have been recently recognized as potent immunoregulatory cells with defined roles in fetomaternal tolerance and immune response to infectious agents in neonates and cancer patients. Here, we show that early-stage EPCs are enriched in anemia, have high levels of arginase 2 (ARG2) and reactive oxygen species (ROS). EPCs expansion in anemic mice leads to the L-arginine depletion in the spleen microenvironment resulting in the suppression of T-cell responses. In humans with anemia, EPCs expand and express both ARG1 and ARG2 that participate in suppressing the proliferation and production of IFN-γ from T-cells. EPCs differentiated from peripheral blood mononuclear cells potently suppress T-cell proliferation and this effect is the most prominent for CD49dhi CD71hiEPCs. The suppressive properties disappear during erythroid differentiation as more differentiated EPCs as well as mature erythrocytes lack significant immunoregulatory properties. Our studies provide a novel insight into the role of EPCs in the regulation of immune response.Abstract Figure

Depletion of Blood Antigen-Presenting Cells by IMMU-114: Therapeutic Potential Against Graft-Versus-Host Disease

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2544-2544
Author(s):  
Xiaochuan Chen ◽  
Chien-Hsing Chang ◽  
Rhona Stein ◽  
David Goldenberg
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Mononuclear Cells ◽  
Therapeutic Potential ◽  
Human Peripheral Blood ◽  
T Cell Immunity ◽  
Peripheral Blood Mononuclear ◽  
Alloreactive T Cells ◽  
Cell Immunity

Abstract Abstract 2544 Background: Graft-versus-host disease (GVHD) is a life-threatening complication of allogeneic hematopoietic stem cell transplantation. Since antigen-presenting cells (APCs) play a critical role in initiating GVHD, selective depletion of host APCs before or during preparative conditioning may yield an improved approach for prevention of GVHD compared to the prevailing therapies, which often compromise the pre-existing T-cell immunity against opportunistic pathogens. IMMU-114 (Immunomedics, Inc.) is an anti-human HLA-DR humanized IgG4 monoclonal antibody (mAb) with a point mutation (Ser241Pro) in the hinge region of the γ4 sequence to avoid the formation of half molecules, and has direct cytotoxicity against a variety of HLA-DR-expressing hematological malignancies. In this study, we investigated the effects of IMMU-114 on the subsets of human blood APCs, and evaluated its effects on the proliferation of alloreactive T cells and preexisting anti-viral memory T-cell immunity in allogeneic mixed leukocyte cultures. Methods: We assessed the effects of IMMU-114 on T cells and all subsets of APCs in human peripheral blood mononuclear cells, including dendritic cells (DCs), B cells, and monocytes. In order to evaluate the therapeutic potential of IMMU-114 against GVHD, we tested the effect of IMMU-114 on the proliferation of alloreactive T cells in allogeneic mixed leukocyte cultures; In order to evaluate the direct effect of IMMU-114 on T cells, we tested the effect of IMMU-114 on the proliferation of already proliferated T cells, and to evaluate the impact of IMMU-114 on preexisting T-cell immunity, we measured the effect of IMMU-114 on HLA-A2-restricted, CMV-specific CD8+ memory T cells by pentamer assay. Results: IMMU-114 depleted almost all subsets of APCs, including dendritic cells (DCs), B cells, and monocytes from human peripheral blood mononuclear cells without affecting the survival of T cells. Specifically, the myeloid DCs type 1 (mDC1) were depleted by 59.2% (P = .0022), myeloid DCs type 2 (mDC2) by 84.8% (P<.0001), plasmacytoid DCs (pDCs) by 52.2% (P = .1927), B cells by 86.2% (P<.0001), and monocytes by 74.7% (P = .01139). In addition, IMMU-114 suppressed the proliferation of alloreactive T cells in mixed leukocyte cultures, yet had no effect on the proliferation of already proliferated T cells. These results suggest that IMMU-114 has therapeutic potential against GVHD, which may be through the depletion of APCs rather than a direct effect on T cells. Importantly, the result demonstrated that CMV-specific, CD8+ memory T cells were preserved in IMMU-114-treated allogeneic mixed leukocyte cultures, suggesting that IMMU-114 may not affect the preexisting anti-viral T-cell immunity, which is essential for immunological control of opportunistic infections following stem cell transplantation. Conclusion: These results indicate that IMMU-114 may be a promising novel agent for prevention and treatment of GVHD through the depletion of APCs. It also supports the investigation of IMMU-114 as a novel component of conditioning regimens for preventing GVHD without alteration of preexisting anti-viral immunity, which would have a distinct advantage over currently available agents for GVHD prevention. (Supported in part by NIH grant PO1-CA103985.) Disclosures: Chang: Immunomedics, Inc.: Employment, Equity Ownership, Patents & Royalties. Goldenberg:Immunomedics, Inc.: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties.

Expression of T-cell receptor Vβ2 and type 1 helper T-cell-related cytokine mRNA in streptococcal pyrogenic exotoxin-C-activated human peripheral blood mononuclear cells

1996 ◽  
Vol 42 (11) ◽  
pp. 1104-1111 ◽  
Author(s):  
Y. Ohara-Nemoto ◽  
M. Kaneko
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Mrna Level ◽  
Helper T Cell ◽  
Peripheral Blood Mononuclear ◽  
Human T Cells ◽  
Blood Mononuclear Cells

Streptococcal pyrogenic exotoxin type C (SPE C) is a member of the bacterial superantigens that are potent stimulants of T cells. We expressed SPE C in Escherichia coli and characterized its selective stimulation properties on human T cells bearing specific Vβ chains of T-cell receptors (TCRs). Cytokine profiles induced by SPE C were also examined. Recombinant SPE C significantly enhanced proliferation of human peripheral blood mononuclear cells (PBMCs) at concentrations as low as 10−12–10−14 M. Reverse transcription of RNA from SPE-C-stimulated PBMCs followed by polymerase chain reaction, revealed selective induction of TCR Vβ2 chain expression. SPE C raised the mRNA level of type 1 helper T cell (TH1) related cytokines, such as interferon γ (IFN-γ), interleukin 2 (IL-2), and tumor necrosis factor β (TNFβ). The expression of TNFα was also increased. In contrast, the increase in mRNA levels of the p35 small fragment of IL-12 and type 2 helper T cell (TH2) related cytokines (i.e., IL-4 and IL-10) was not significantly affected by SPE C. The mRNA level of proinflammatory cytokine IL-6 was increased marginally. Consistent with the mRNA accumulation, protein concentrations of IFNγ, IL-2, and TNF were increased in SPE-C-stimulated PBMCs, but IL-4 was not. From these results, we conclude that the stimuli of SPE C preferentially causes the TH1 responses in human T cells bearing TCR Vβ2.Key words: streptococcal pyrogenic exotoxin C, Streptococcus pyogenes, T cells, cytokine, superantigen.

Dexamethasone, but not meloxicam, suppresses proliferation of bovine CD25+CD4+ and CD25-CD4+ T cells

2013 ◽  
Vol 16 (2) ◽  
pp. 219-222 ◽  
Author(s):  
T. Maślanka ◽  
J.J. Jaroszewski
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
Mononuclear Cells ◽  
Flow Cytometry Analysis ◽  
Peripheral Blood Mononuclear ◽  
Proliferative Effect ◽  
Blood Mononuclear Cells ◽  
Cell Subpopulations ◽  
Incorporation Assay ◽  
T Cell Subpopulations

Abstract Recently, we found that dexamethasone caused a depletion of CD25-CD4+ T cells, but it increased the number of CD25highCD4+ and CD25lowCD4+ T cells. We also determined meloxicam-induced increase in the number of CD25highCD4+ T cells. In view of this, and taking into consideration the latest reports indicating that meloxicam shows an anti-proliferative effect on bovine peripheral blood mononuclear cells, it was considered purposeful to determine the effect of both drugs on proliferation of bovine CD25highCD4+, CD25lowCD4+ and CD25-CD4+ T cells. Flow cytometry analysis and 5-bromo-2’-deoxyuridine incorporation assay were applied to detect the cell proliferation. It was demonstrated that dexamethasone, but not meloxicam, significantly reduced cell proliferation within all three evaluated CD4+ T cell subpopulations. Thus, the depletion of CD25-CD4+ T cells by treatment with dexamethasone can partly be the effect of the anti-proliferative action of the drug, however, dexamethasone-induced increase in the number of CD25highCD4+ and CD25lowCD4+ T cells cannot be the result of enhanced proliferation of these cells.

scholarly journals T-Cell Receptor Vβ Repertoire CDR3 Length Diversity Differs within CD45RA and CD45RO T-Cell Subsets in Healthy and Human Immunodeficiency Virus-Infected Children

2000 ◽  
Vol 7 (6) ◽  
pp. 953-959 ◽  
Author(s):  
Zhong Chen Kou ◽  
Joshua S. Puhr ◽  
Mabel Rojas ◽  
Wayne T. McCormack ◽  
Maureen M. Goodenow ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mononuclear Cells ◽  
Cell Receptor ◽  
T Cell Subsets ◽  
Cdr3 Length ◽  
Immunodeficiency Virus ◽  
Tcr Repertoire ◽  
Cell Subpopulations ◽  
T Cell Subpopulations

ABSTRACT The T-cell receptor (TCR) CDR3 length heterogeneity is formed during recombination of individual Vβ gene families. We hypothesized that CDR3 length diversity could be used to assess the fundamental differences within the TCR repertoire of CD45RA and CD45RO T-cell subpopulations. By using PCR-based spectratyping, nested primers for all 24 human Vβ families were developed to amplify CDR3 lengths in immunomagnetically selected CD45RA and CD45RO subsets within both CD4+ and CD8+ T-cell populations. Umbilical cord blood mononuclear cells or peripheral blood mononuclear cells obtained from healthy newborns, infants, and children, as well as human immunodeficiency virus (HIV)-infected children, were analyzed. All T-cell subsets from newborn and healthy children demonstrated a Gaussian distribution of CDR3 lengths in separated T-cell subsets. In contrast, HIV-infected children had a high proportion of predominant CDR3 lengths within both CD45RA and CD45RO T-cell subpopulations, most commonly in CD8+ CD45RO T cells. Sharp differences in clonal dominance and size distributions were observed when cells were separated into CD45RA or CD45RO subpopulations. These differences were not apparent in unfractionated CD4+ or CD8+ T cells from HIV-infected subjects. Sequence analysis of predominant CDR3 lengths revealed oligoclonal expansion within individual Vβ families. Analysis of the CDR3 length diversity within CD45RA and CD45RO T cells provides a more accurate measure of disturbances in the TCR repertoire than analysis of unfractionated CD4 and CD8 T cells.

scholarly journals Identification of the Lymphoma-Initiating Cell Population in a T Cell Lymphoma Mouse Model Resembling Human Anaplastic Large Cell Lymphoma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2213-2213
Author(s):  
Cathrin Klingeberg ◽  
Stefanie Kreutmair ◽  
Cornelius Miething ◽  
Marie Follo ◽  
Christian Peschel ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Cell Population ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Double Negative ◽  
Cell Subpopulations ◽  
T Cell Subpopulations

Abstract In 60% of anaplastic large cell lymphoma (ALCL) patients a translocation t(2;5) (p23;q35) is found, which results in NPM-ALK fusion gene expression and constitutive activation of the ALK tyrosine kinase. Immunophenotypic characterization of human ALCLs revealed highly CD30-positive cells of T- or Null-cell-origin. However, the origin of the lymphoma initiating cell population as well as NPM-ALK signal transduction in course of the disease remains unclear. In this regard, we established a retroviral murine bone marrow transplantation model resembling human ALCL. Therefore we use an inducible Cre/loxP system where NPM-ALK expression is restricted to early T cells. We infected bone marrow of Lck-Cre transgenic mice with our MSCV-Stop-NPM-ALK-IRES-EGFP vector and transplanted it into lethally irradiated recipient mice. With a latency of 4-5 months, these mice developed Thy1.2-positive lymphomas and died from neoplastic T cell infiltration of bone marrow and lymphatic organs. Immunophenotypic analysis confirmed T cell origin of the lymphomas with the characteristic high CD30 expression. Staining of the T cell subpopulations demonstrated high NPM-ALK expression in immature CD4-/CD8- double negative T cells and undifferentiated CD4+/CD8+ double positive T cells. Interestingly, FACS-staining for the proliferation marker Ki-67 as well as the activation marker CD30 revealed highest expression in the CD4-/CD8- double negative T cells. Therefore we hypothesized that the lymphoma-initiating cell must be within this early T cell population. To substantiate our hypothesis we performed secondary transplantations with sorted T cell subpopulations and indeed, only the CD4-/CD8- double negative population was able to initiate T cell lymphoma in the recipient mice. Immunophenotypic characterization of the lymphoma population of these secondary transplanted mice revealed undifferentiated T cells of all CD4/CD8 subtypes, which argues for the existence of a lymphoma initiating cell population, which can still partly differentiate. Interestingly the CD4-/CD8- double negative lymphoma population aberrantly expressed the T cell receptor alpha/beta chain, which may allow these early T cells to establish a systemic lymphoma. Further analysis of the lymphoma population showed lymphatic precursors (CLP) as well as multipotent progenitors (MMP) and haematopoetic stem cells (LSK), which suggests early bone marrow or thymic progenitor cells as the pool of the lymphoma-initiating cell population. We therefore were able to prove the existence of lymphoma initiating stem cells in a highly relevant NPM-ALK positive CD30 expressing mouse model of ALCL. Further analysis will give insides into eradication of the identified lymphoma stem cell population by clinical relevant NPM-ALK inhibitors and CD30 immunotoxins. Disclosures No relevant conflicts of interest to declare.

scholarly journals Antibody-Dependent Cellular Cytotoxicity against Primary HIV-Infected CD4+T Cells Is Directly Associated with the Magnitude of Surface IgG Binding

2012 ◽  
Vol 86 (16) ◽  
pp. 8672-8680 ◽  
Author(s):  
Adjoa Smalls-Mantey ◽  
Nicole Doria-Rose ◽  
Rachel Klein ◽  
Andy Patamawenu ◽  
Stephen A. Migueles ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Cellular Cytotoxicity ◽  
Peripheral Blood Mononuclear ◽  
Igg Binding ◽  
Normal Human Peripheral Blood ◽  
Hiv 1

Antibody (Ab)-dependent cellular cytotoxicity (ADCC) is thought to potentially play a role in vaccine-induced protection from HIV-1. The characteristics of such antibodies remain incompletely understood. Furthermore, correlates between ADCC and HIV-1 immune status are not clearly defined. We screened the sera of 20 HIV-1-positive (HIV-1+) patients for ADCC. Normal human peripheral blood mononuclear cells were used to derive HIV-infected CD4+T cell targets and autologous, freshly isolated, natural killer (NK) cells in a novel assay that measures granzyme B (GrB) and HIV-1-infected CD4+T cell elimination (ICE) by flow cytometry. We observed that complex sera mediated greater levels of ADCC than anti-HIV-1 envelope glycoprotein (Env)-specific monoclonal antibodies and serum-mediated ADCC correlated with the amount of IgG and IgG1 bound to HIV-1-infected CD4+T cells. No correlation between ADCC and viral load, CD4+T cell count, or neutralization of HIV-1SF162or other primary viral isolates was detected. Sera pooled from clade B HIV-1+individuals exhibited breadth in killing targets infected with HIV-1 from clades A/E, B, and C. Taken together, these data suggest that the total amount of IgG bound to an HIV-1-infected cell is an important determinant of ADCC and that polyvalent antigen-specific Abs are required for a robust ADCC response. In addition, Abs elicited by a vaccine formulated with immunogens from a single clade may generate a protective ADCC responsein vivoagainst a variety of HIV-1 species. Increased understanding of the parameters that dictate ADCC against HIV-1-infected cells will inform efforts to stimulate ADCC activity and improve its potency in vaccinees.

Class I–unrestricted noncytotoxic anti–HTLV-I activity of CD8+ T cells

Blood ◽  
2000 ◽  
Vol 96 (5) ◽  
pp. 1994-1995 ◽  
Author(s):  
Masako Moriuchi ◽  
Hiroyuki Moriuchi
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Mononuclear Cells ◽  
Membrane Filter ◽  
Cd8 T Cell ◽  
Class I ◽  
Type I ◽  
Peripheral Blood Mononuclear ◽  
Permeable Membrane

Abstract Although it is widely believed that viral clearance is mediated principally by the destruction of infected cells by cytotoxic T cells, noncytolytic antiviral activity of CD8+ T cells may play a role in preventing the progression to disease in infections with immunodeficiency viruses and hepatitis B virus. We demonstrate here that (1) replication of human T-lymphotropic virus type I (HTLV-I) is more readily detected from CD8+ T-cell–depleted (CD8−) peripheral blood mononuclear cells (PBMCs) of healthy HTLV-I carriers than from unfractionated PBMCs, (2) cocultures of CD8− PBMCs with autologous or allogeneic CD8+ T cells suppressed HTLV-I replication, and (3) CD8+ T-cell anti-HTLV-I activity is not abrogated intrans-well cultures in which CD8+ cells are separated from CD8− PBMCs by a permeable membrane filter. These results suggest that class I-unrestricted noncytolytic anti–HTLV-I activity is mediated, at least in part by a soluble factor(s), and may play a role in the pathogenesis of HTLV-I infection.

scholarly journals Alterations in regulatory T cells and immune checkpoint molecules in pancreatic cancer patients receiving FOLFIRINOX or gemcitabine plus nab-paclitaxel

2021 ◽  
Author(s):  
L. Sams ◽  
S. Kruger ◽  
V. Heinemann ◽  
D. Bararia ◽  
S. Haebe ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Cd8 T Cells ◽  
Mononuclear Cells ◽  
Progression Free Survival ◽  
Ductal Adenocarcinoma ◽  
Immune Checkpoints ◽  
Prognostic Information ◽  
Peripheral Blood Mononuclear

Abstract Purpose This pilot study aimed on generating insight on alterations in circulating immune cells during the use of FOLFIRINOX and gemcitabine/nab-paclitaxel in pancreatic ductal adenocarcinoma (PDAC). Patients and methods Peripheral blood mononuclear cells were isolated before and 30 days after initiation of chemotherapy from 20 patients with advanced PDAC. Regulatory T cells (FoxP3+) and immune checkpoints (PD-1 and TIM-3) were analyzed by flow cytometry and immunological changes were correlated with clinical outcome. Results Heterogeneous changes during chemotherapy were observed in circulating T-cell subpopulations with a pronounced effect on PD-1+ CD4+/CD8+ T cells. An increase in FoxP3+ or PD-1+ T cells had no significant effect on survival. An increase in TIM3+/CD8+ (but not TIM3+/CD4+) T cells was associated with a significant inferior outcome: median progression-free survival in the subgroup with an increase of TIM-3+/CD8+ T cells was 6.0 compared to 14.0 months in patients with a decrease/no change (p = 0.026); corresponding median overall survival was 13.0 and 20.0 months (p = 0.011), respectively. Conclusions Chemotherapy with FOLFIRNOX or gemcitabine/nab-paclitaxel induces variable changes in circulating T-cell populations that may provide prognostic information in PDAC.

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