scholarly journals Significant decrease in cord blood (CB) versus adult peripheral blood (APB) monocyte (Mo)–derived dendritic cell (DC) gene and protein expression patterns and T cell functional activation: Insight into immaturity of CB cellular immunity

2006 ◽  
Vol 12 (2) ◽  
pp. 52-53
Author(s):  
H. Jiang ◽  
C. Wade-Harris ◽  
L. Baxi ◽  
M.S. Cairo
Keyword(s):  
T Cell ◽  
Dendritic Cell ◽  
Protein Expression ◽  
Cord Blood ◽  
Cellular Immunity ◽  
Peripheral Blood ◽  
Expression Patterns ◽  
Gene And Protein Expression ◽  
Insight Into ◽  
Adult Peripheral Blood

Persistence of naive CD45RA+ regulatory T cells in adult life

Blood ◽  
2006 ◽  
Vol 107 (7) ◽  
pp. 2830-2838 ◽  
Author(s):  
Nabila Seddiki ◽  
Brigitte Santner-Nanan ◽  
Stuart G. Tangye ◽  
Stephen I. Alexander ◽  
Michael Solomon ◽  
...  
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
T Cell ◽  
Regulatory T Cells ◽  
Cord Blood ◽  
Peripheral Blood ◽  
Cell Subset ◽  
Human Infant ◽  
Wide Range ◽  
Adult Peripheral Blood

AbstractRegulatory T cells (TREGs) constitutively expressing CD4, CD25, and the transcription factor Foxp3 can prevent a wide range of experimental and spontaneous autoimmune diseases in mice. In humans, CD4+CD25bright T cells, predominantly within the CD45RO+ activated/memory subset in adults and the CD45RA+ naive T-cell subset in infants, are considered to be the equivalent subset. Using novel combinations of monoclonal antibodies (mAbs), we examined expression of CD25 in human infant thymus, cord blood, adult peripheral blood, lymph node, and spleen. In addition to the CD4+CD25bright T cells, subfractionation on the basis of CD45 splice variants indicated that all samples contained a second distinct population of cells expressing a slightly lower level of CD25. In adult peripheral blood, this population expressed a naive CD45RA+ phenotype. The corresponding population in lymph node, spleen, and cord blood showed some evidence of activation, and expressed markers characteristic of TREGs, such as cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). Sorted CD4+CD25+CD45RA+ T cells from both cord and adult blood expressed very high levels of mRNA for Foxp3 and manifested equivalent suppressive activity in vitro, indicating that they are bone fide members of the regulatory T-cell lineage. Targeting naive TREGs in adults may offer new means of preventing and treating autoimmune disease.

scholarly journals Decreased interleukin-12 (IL-12) from activated cord versus adult peripheral blood mononuclear cells and upregulation of interferon- gamma, natural killer, and lymphokine-activated killer activity by IL- 12 in cord blood mononuclear cells

Blood ◽  
1996 ◽  
Vol 88 (3) ◽  
pp. 945-954 ◽  
Author(s):  
SM Lee ◽  
Y Suen ◽  
L Chang ◽  
V Bruner ◽  
J Qian ◽  
...  
Keyword(s):  
Cord Blood ◽  
Cellular Immunity ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Interleukin 12 ◽  
Ifn Gamma ◽  
Impaired Ability ◽  
Blood Mononuclear Cells ◽  
Nk Cytotoxicity ◽  
Adult Peripheral Blood

Abstract Interleukin-12 (IL-12) is a critical cytokine regulating natural killer (NK) and T-cell function. We hypothesized that the impaired ability of cord blood (CB) to produce normal adult levels of IL-12 in response to stimulation may contribute to the immaturity of CB immunity. Furthermore, exogenous IL-12 may compensate for the immaturity in CB cellular immunity and have the potential for immunotherapy post cord blood transplantation. We compared the expression and production of IL- 12 from activated cord versus adult mononuclear cells (MNC), regulatory mechanisms associated with IL-12 expression in CB MNC, and the effects of IL-12 on induction of CB interferon (IFN)-gamma production, NK, and lymphokine-activated killer (LAK) cytotoxicity. Northern analysis and enzyme-linked immunosorbent assay were performed in lipopolysaccharide (LPS)-stimulated CB and adult peripheral blood (APB) MNC. IL-12 mRNA expression was induced within 6 hours with LPS (10 micrograms/ml) and reached peak levels at 12 hours in both CB and APB MNC. However, IL-12 mRNA expression and protein accumulation in CB MNC were 35.8% +/- 4.84% (12 hours, n = 11, P < .05), and 17.6% +/- 1.7% (24, 72, 96 hours, n = 9, P < .05) respectively, when compared with APB MNC. Nuclear run-on assays showed no differences between CB and APB MNC in both the basal levels of transcription and the degree of transcriptional activation. However, the half-life of IL-12 p40 mRNA was approximately threefold lower in activated CB MNC than in activated APB MNC (CB: 114 +/- 3.0 minutes v APB: 353 +/- 7.8 minutes, n = 3, P < .05). Exogenous IL-12 (10 U/mL) induced a significant increase of IFN-gamma from both CB and APB MNC (24 hours, 72 hours, P < .05, n = 3). The stimulated CB IFN- gamma level reached comparable levels produced by unstimulated APB. IL- 12 treatment also significantly enhanced CB NK cytotoxicity against K562 and NB-100 cell lines to the comparable levels of APB (P < .05, n = 4). CB MNC was more responsive to IL-12 stimulation with respect to IFN-gamma production, NK, and LAK cytotoxicity when compared with APB. The present study suggests that IL-12 mRNA and protein expression is decreased in activated CB. This discrepancy in IL-12 production is secondary, at least in part, to the altered posttranscriptional regulation. The impaired, ability of CB MNC to produce IL-12 in response to stimulation may contribute to the decrease in IFN-gamma production and NK cytotoxicity. However, IL-12 enhanced IFN-gamma and NK activity in CB MNC up to the comparable levels of APB MNC. These findings suggest that reduced expression and production of IL-12 from activated CB may contribute to the immaturity in CB cellular immunity and contribute, in part, to decreased graft-versus-host disease following CB stem cell transplantation.

scholarly journals BCL11B Upregulates the Expression of NF-κB in T Cells Stimulated with SEA

2021 ◽  
Author(s):  
Yuhui Yan ◽  
Senlin Wang ◽  
Chen Lin
Keyword(s):  
T Cells ◽  
Transcription Factors ◽  
T Cell ◽  
Protein Expression ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Jurkat Cells ◽  
Cell Leukaemia ◽  
Normal Peripheral Blood ◽  
Gene And Protein Expression

Abstract BackgroundNF-κB is one of the most important inflammatory mediators in the tumour microenvironment promotes inflammation-induced cancer. Many studies report that NF-κB is activated in many kinds of leukaemia, so that some researchers by inhibiting NF-κB to treat leukaemia. The overexpression of BCL11B has been primarily reported in T cell malignancies. Some studies have reported that BCL11B is a potential transcriptional repressor which has several splice isoforms. MiR-21-5p promotes cell proliferation by targeting BCL11B in Thp-1 human monocytes. Both NF-κB and BCL11B transcription factors are related to inflammation and leukaemia. Whether there is correlation between NF-κB and BCL11B transcription factors? If BCL11B is a potential important transcription factor in treatment of T lymphocyte leukaemia? In this study, we stimulated Jurkat cells and normal peripheral blood T cells with staphylococcal enterotoxin A(SEA), and we detected the expression of both the BCL11B and NF-κB genes and their respective proteins at different stimulation times. Then, the BCL11B gene was suppressed by BCL11B-siRNA and detected at another stimulation time. ResultsWe found that the mRNA expression of BCL11B and NF-κB increased in two kinds of T cell lines over time which stimulated by SEA or PMA+IO. A similar result was confirmed for BCL11B and NF-κB protein expression. While the expression of the NF-κB protein did not increase on equal conditions in the BCL11B-knockdown group. ConclusionOur result suggested that the gene and protein expression levels of both BCL11B and NF-κB were related, and BCL11B regulates NF-κB expression in Jukat cells and healthy human peripheral blood through the TCR signalling pathway. This study reveals that BCL11B can be used as a new therapeutic target for chronic inflammation and T cell leukaemia pathogenesis.

scholarly journals Decreased interleukin-12 (IL-12) from activated cord versus adult peripheral blood mononuclear cells and upregulation of interferon- gamma, natural killer, and lymphokine-activated killer activity by IL- 12 in cord blood mononuclear cells

Blood ◽  
1996 ◽  
Vol 88 (3) ◽  
pp. 945-954 ◽  
Author(s):  
SM Lee ◽  
Y Suen ◽  
L Chang ◽  
V Bruner ◽  
J Qian ◽  
...  
Keyword(s):  
Cord Blood ◽  
Cellular Immunity ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Interleukin 12 ◽  
Ifn Gamma ◽  
Impaired Ability ◽  
Blood Mononuclear Cells ◽  
Nk Cytotoxicity ◽  
Adult Peripheral Blood

Interleukin-12 (IL-12) is a critical cytokine regulating natural killer (NK) and T-cell function. We hypothesized that the impaired ability of cord blood (CB) to produce normal adult levels of IL-12 in response to stimulation may contribute to the immaturity of CB immunity. Furthermore, exogenous IL-12 may compensate for the immaturity in CB cellular immunity and have the potential for immunotherapy post cord blood transplantation. We compared the expression and production of IL- 12 from activated cord versus adult mononuclear cells (MNC), regulatory mechanisms associated with IL-12 expression in CB MNC, and the effects of IL-12 on induction of CB interferon (IFN)-gamma production, NK, and lymphokine-activated killer (LAK) cytotoxicity. Northern analysis and enzyme-linked immunosorbent assay were performed in lipopolysaccharide (LPS)-stimulated CB and adult peripheral blood (APB) MNC. IL-12 mRNA expression was induced within 6 hours with LPS (10 micrograms/ml) and reached peak levels at 12 hours in both CB and APB MNC. However, IL-12 mRNA expression and protein accumulation in CB MNC were 35.8% +/- 4.84% (12 hours, n = 11, P < .05), and 17.6% +/- 1.7% (24, 72, 96 hours, n = 9, P < .05) respectively, when compared with APB MNC. Nuclear run-on assays showed no differences between CB and APB MNC in both the basal levels of transcription and the degree of transcriptional activation. However, the half-life of IL-12 p40 mRNA was approximately threefold lower in activated CB MNC than in activated APB MNC (CB: 114 +/- 3.0 minutes v APB: 353 +/- 7.8 minutes, n = 3, P < .05). Exogenous IL-12 (10 U/mL) induced a significant increase of IFN-gamma from both CB and APB MNC (24 hours, 72 hours, P < .05, n = 3). The stimulated CB IFN- gamma level reached comparable levels produced by unstimulated APB. IL- 12 treatment also significantly enhanced CB NK cytotoxicity against K562 and NB-100 cell lines to the comparable levels of APB (P < .05, n = 4). CB MNC was more responsive to IL-12 stimulation with respect to IFN-gamma production, NK, and LAK cytotoxicity when compared with APB. The present study suggests that IL-12 mRNA and protein expression is decreased in activated CB. This discrepancy in IL-12 production is secondary, at least in part, to the altered posttranscriptional regulation. The impaired, ability of CB MNC to produce IL-12 in response to stimulation may contribute to the decrease in IFN-gamma production and NK cytotoxicity. However, IL-12 enhanced IFN-gamma and NK activity in CB MNC up to the comparable levels of APB MNC. These findings suggest that reduced expression and production of IL-12 from activated CB may contribute to the immaturity in CB cellular immunity and contribute, in part, to decreased graft-versus-host disease following CB stem cell transplantation.

scholarly journals Comparative Study of Regulatory T Cell Function of HumanCD25+CD4+T Cells from Thymocytes, Cord Blood, and Adult Peripheral Blood

2008 ◽  
Vol 2008 ◽  
pp. 1-12 ◽  
Author(s):  
Wakae Fujimaki ◽  
Nozomu Takahashi ◽  
Kei Ohnuma ◽  
Masayoshi Nagatsu ◽  
Hiromi Kurosawa ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cord Blood ◽  
T Cell Activation ◽  
Peripheral Blood ◽  
Expression Level ◽  
Regulatory Function ◽  
Suppressive Activity ◽  
Functional Differences ◽  
Adult Peripheral Blood

CD25+CD4+regulatory T cells suppress T cell activation and regulate multiple immune reactions in in vitro and in vivo studies. To define the regulatory function of humanCD25+CD4+T cells at various stages of maturity, we investigated in detail the functional differences ofCD25+CD4+T cells from thymocytes, cord blood (CB), and adult peripheral blood (APB). CBCD25+CD4+T cells displayed low-FOXP3 protein expression level and had no suppressive activity. In contrast,CD25+CD4+T cells from thymocytes or APB expressed high expression level of FOXP3 protein associated with significant suppressive activity. Although CBCD25+CD4+T cells exhibited no suppressive activity, striking suppressive activity was observed following expansion in culture associated with increased FOXP3 expression and a shift from theCD45RA+to theCD45RA−phenotype. These functional differences inCD25+CD4+T cells from Thy, CB, and APB hence suggest a pathway of maturation for Treg in the peripheral immune system.

scholarly journals AB0037 EXPRESSION OF NEGATIVE CHECKPOINT MOLECULES BTLA AND HVEM IS DYSREGULATED IN AUTOIMMUNE DISEASES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1321.1-1321
Author(s):  
S. Nagpal ◽  
S. Cole ◽  
A. Floudas ◽  
M. Wechalekar ◽  
Q. Song ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Autoimmune Disease ◽  
Autoimmune Diseases ◽  
Immune Checkpoint ◽  
Peripheral Blood ◽  
Expression Patterns ◽  
Myeloid Cell ◽  
Dependent Manner ◽  
Research Support

Background:Immune checkpoint blockade with agents targeting CTLA4 and PD-1/PD-L1 alone or in combination has demonstrated exceptional efficacy in multiple cancer types by “unleashing” the cytotoxic action of quiescent, tumor-infiltrating T cells. However, the therapeutic action of these immunotherapies goes hand in hand with the loss of immune tolerance and appearance of immune-related adverse events such as colitis, arthralgia and inflammatory arthritis in responsive patients. Therefore, immune checkpoint molecules have been proposed as targets for the treatment of autoimmune diseases.Objectives:Herein, we interrogate the potential of BTLA/HVEM axis as a target for restoring immune homeostasis in rheumatoid arthritis (RA), Systemic Lupus Erythematosus (SLE) and Sjogren’s Syndrome (SjS) by examining their expression patterns in autoimmune disease tissues.Methods:Message and protein expression of BTLA and HVEM were examined in RA and SLE synovial tissues, SLE cutaneous lesions, SjS salivary glands and peripheral blood samples of autoimmune disease by RNA sequencing and flow cytometry.Results:Tissue dysregulation of the BTLA-HVEM axis was observed: Increased BTLA RNA level in RA synovium, SLE-affected skin, and SjS salivary gland samples, whereas HVEM level was affected only in the RA synovium when compared to unaffected tissues. Detailed immunophenotyping of B, T, and myeloid cell populations in RA, SLE, SjS and healthy control PBMCs revealed differential modulation of the BTLA+ or HVEM+ immune cell subsets in a disease-context dependent manner. SjS patients showed an overall decrease in memory B cells and most of the BTLA+ B cell subsets while a decrease in HVEM+ B cells was observed only in SLE PBMC samples and not RA and SLE samples. Immunophenotyping with a T cell panel exhibited decreased BTLA and HVEM expression on T cell subsets in SjS and SLE but not in RA patients. In addition, protein levels of HVEM were differentially decreased in SLE myeloid cell subsets. Finally, we demonstrate tissue-specific surface expression patterns of BTLA in RA and SLE samples: higher surface BTLA levels on RA and SLE PBMC B cells than matched tissue-derived B cells.Conclusion:Our results demonstrate a dysregulation of the BTLA/HVEM axis in either lesional tissue or peripheral blood in an autoimmune disease context-dependent manner. These results also indicate the potential of targeting BTLA-HVEM axis for the treatment of multiple autoimmune diseases.Disclosure of Interests:Sunil Nagpal Shareholder of: Janssen Pharmaceuticals, Employee of: Janssen Pharmaceuticals, Suzanne Cole Shareholder of: Janssen Research & Development employee, Employee of: Janssen Research & Development employee, Achilleas Floudas: None declared, Mihir Wechalekar Grant/research support from: Grant from Janssen Research & Development, Qingxuan Song Shareholder of: Employee of Janssen Research, Employee of: Employee of Janssen Research, Tom Gordon: None declared, Roberto Caricchio Grant/research support from: Financial grant from Janssen Research & Development, Douglas Veale: None declared, Ursula Fearon: None declared, Navin Rao Shareholder of: Janssen Pharmaceuticals, Employee of: Janssen Pharmaceuticals, Ling-Yang Hao Shareholder of: Employee of Janssen Research, Employee of: Employee of Janssen Research

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