scholarly journals Myeloid-Derived Suppressor Cells Therapy Enhance Immunoregulatory Properties in Acute Graft Versus Host Diseas with Combination of Regulatory T Cells

2020 ◽  
Author(s):  
Min-Jung Park ◽  
Jin-Ah Baek ◽  
Se-Young Kim ◽  
Kyung-Ah Jung ◽  
Jeong Won Choi ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Therapy ◽  
B Cell ◽  
Immune Tolerance ◽  
Cell Subset ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Graft Versus Host ◽  
Acute Graft

Abstract Background: Myeloid-derived suppressor cells (MDSCs) play a critical role in modulating the immune response and suppressing autoimmunity and transplantation. Regulatory T cells (Tregs) exert therapeutic potential due to their immunomodulatory properties, which have been demonstrated both in vitro and in clinical trials. Cell-based therapy for acute Graft-versus-host disease (aGVHD) may enable induction of donor-specific tolerance in the preclinical setting. Methods: We investigated whether the immunoregulatory activity of the combination of MDSCs and Tregs on T cell and B cell subset and alloreactive T cell response. We evaluated the therapeutic effects of combined cell therapy for aGVHD following MHC-mismatched bone marrow transplantation. We compared histologic analysis from the target tissues of each groups were and immune cell population by flow cytometric analysisResults: We report a novel approach to inducing immune tolerance using a combination of donor-derived MDSCs and Tregs. The combined cell-therapy modulated in vitro the proliferation of alloreactive T cells and the Treg/Th17 balance in mice system. Systemic infusion of MDSCs and Tregs ameliorated serverity and inflammation of aGVHD by reducing the populations of proinflammatory Th1/Th17 cells and the expression of proinflammatory cytokines in target tissue. The combined therapy promoted the differentiation of allogeneic T cells toward Foxp3+Tregs and IL-10-producing regulatory B cells. The combination treatment control also activated human T and B cell subset.Conclusions: Therefore, the combination of MDSCs and Tregs has immunomodulatory activity and induces immune tolerance to prevent of aGVHD severity. This could lead to the development of new clinical approaches to the prevent aGVHD.

scholarly journals Myeloid-derived suppressor cells therapy enhance immunoregulatory properties in acute graft versus host diseas with combination of regulatory T cells

2020 ◽  
Author(s):  
Min-Jung Park ◽  
Jin-Ah Baek ◽  
Se-Young Kim ◽  
Kyung-Ah Jung ◽  
Jeong Won Choi ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Therapy ◽  
B Cell ◽  
Immune Tolerance ◽  
Cell Subset ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Graft Versus Host ◽  
Acute Graft

Abstract Background: Myeloid-derived suppressor cells (MDSCs) play a critical role in modulating the immune response and promoting immune tolerance in models of autoimmunity and transplantation. Regulatory T cells (Tregs) exert therapeutic potential due to their immunomodulatory properties, which have been demonstrated both in vitro and in clinical trials. Cell-based therapy for acute graft-versus-host disease (aGVHD) may enable induction of donor-specific tolerance in the preclinical setting. Methods: We investigated whether the immunoregulatory activity of the combination of MDSCs and Tregs on T cell and B cell subset and alloreactive T cell response. We evaluated the therapeutic effects of combined cell therapy for a murine aGVHD model following MHC-mismatched bone marrow transplantation. We compared histologic analysis from the target tissues of each groups were and immune cell population by flow cytometric analysisResults: We report a novel approach to inducing immune tolerance using a combination of donor-derived MDSCs and Tregs. The combined cell-therapy modulated in vitro the proliferation of alloreactive T cells and the Treg/Th17 balance in mice and human system. Systemic infusion of MDSCs and Tregs ameliorated serverity and inflammation of aGVHD mouse model by reducing the populations of proinflammatory Th1/Th17 cells and the expression of proinflammatory cytokines in target tissue. The combined therapy promoted the differentiation of allogeneic T cells toward Foxp3+Tregs and IL-10-producing regulatory B cells. The combination treatment control also activated human T and B cell subset.Conclusions: Therefore, the combination of MDSCs and Tregs has immunomodulatory activity and induces immune tolerance to prevent of aGVHD severity. This could lead to the development of new clinical approaches to the prevent aGVHD.

scholarly journals Myeloid-derived suppressor cells therapy enhance immunoregulatory properties in acute graft versus host diseas with combination of regulatory T cells

2020 ◽  
Author(s):  
Min-Jung Park ◽  
Jin-Ah Baek ◽  
Se-Young Kim ◽  
Kyung-Ah Jung ◽  
Jeong Won Choi ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Therapy ◽  
B Cell ◽  
Immune Tolerance ◽  
Cell Subset ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Graft Versus Host ◽  
Acute Graft

Abstract Background: Myeloid-derived suppressor cells (MDSCs) play a critical role in modulating the immune response and promoting immune tolerance in models of autoimmunity and transplantation. Regulatory T cells (Tregs) exert therapeutic potential due to their immunomodulatory properties, which have been demonstrated both in vitro and in clinical trials. Cell-based therapy for acute graft-versus-host disease (aGVHD) may enable induction of donor-specific tolerance in the preclinical setting. Methods: We investigated whether the immunoregulatory activity of the combination of MDSCs and Tregs on T cell and B cell subset and alloreactive T cell response. We evaluated the therapeutic effects of combined cell therapy for a murine aGVHD model following MHC-mismatched bone marrow transplantation. We compared histologic analysis from the target tissues of each groups were and immune cell population by flow cytometric analysisResults: We report a novel approach to inducing immune tolerance using a combination of donor-derived MDSCs and Tregs. The combined cell-therapy modulated in vitro the proliferation of alloreactive T cells and the Treg/Th17 balance in mice and human system. Systemic infusion of MDSCs and Tregs ameliorated serverity and inflammation of aGVHD mouse model by reducing the populations of proinflammatory Th1/Th17 cells and the expression of proinflammatory cytokines in target tissue. The combined therapy promoted the differentiation of allogeneic T cells toward Foxp3+Tregs and IL-10-producing regulatory B cells. The combination treatment control also activated human T and B cell subset.Conclusions: Therefore, the combination of MDSCs and Tregs has immunomodulatory activity and induces immune tolerance to prevent of aGVHD severity. This could lead to the development of new clinical approaches to the prevent aGVHD.

scholarly journals Myeloid-derived suppressor cells therapy enhance immunoregulatory properties in acute graft versus host disease with combination of regulatory T cells

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Min-Jung Park ◽  
Jin-Ah Baek ◽  
Se-Young Kim ◽  
Kyung-Ah Jung ◽  
Jeong Won Choi ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Therapy ◽  
Immune Tolerance ◽  
Graft Versus Host Disease ◽  
Cell Subset ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Graft Versus Host ◽  
Acute Graft

Abstract Background Myeloid-derived suppressor cells (MDSCs) play a critical role in modulating the immune response and promoting immune tolerance in models of autoimmunity and transplantation. Regulatory T cells (Tregs) exert therapeutic potential due to their immunomodulatory properties, which have been demonstrated both in vitro and in clinical trials. Cell-based therapy for acute graft-versus-host disease (aGVHD) may enable induction of donor-specific tolerance in the preclinical setting. Methods We investigated whether the immunoregulatory activity of the combination of MDSCs and Tregs on T cell and B cell subset and alloreactive T cell response. We evaluated the therapeutic effects of combined cell therapy for a murine aGVHD model following MHC-mismatched bone marrow transplantation. We compared histologic analysis from the target tissues of each groups were and immune cell population by flow cytometric analysis. Results We report a novel approach to inducing immune tolerance using a combination of donor-derived MDSCs and Tregs. The combined cell-therapy modulated in vitro the proliferation of alloreactive T cells and the Treg/Th17 balance in mice and human system. Systemic infusion of MDSCs and Tregs ameliorated serverity and inflammation of aGVHD mouse model by reducing the populations of proinflammatory Th1/Th17 cells and the expression of proinflammatory cytokines in target tissue. The combined therapy promoted the differentiation of allogeneic T cells toward Foxp3 + Tregs and IL-10-producing regulatory B cells. The combination treatment control also activated human T and B cell subset. Conclusions Therefore, the combination of MDSCs and Tregs has immunomodulatory activity and induces immune tolerance to prevent of aGVHD severity. This could lead to the development of new clinical approaches to the prevent aGVHD.

scholarly journals CD1c but neither CD1a nor CD1b molecules are expressed on normal, activated, and malignant human B cells: identification of a new B-cell subset

Blood ◽  
1988 ◽  
Vol 72 (1) ◽  
pp. 241-247 ◽  
Author(s):  
D Delia ◽  
G Cattoretti ◽  
N Polli ◽  
E Fontanella ◽  
A Aiello ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
De Novo ◽  
Cell Subset ◽  
Ultrastructural Level ◽  
Cytoplasmic Staining ◽  
Clear Cut ◽  
Hodgkin's Lymphomas

Abstract The CD1 cluster of monoclonal antibodies (MoAbs) CD1a, CD1b, and CD1c, identifies molecules that are differentially expressed on hematopoietic and nonhematopoietic tissues. Our earlier finding that the mantle zone (MZ) but not the germinal center (GC) of normal lymph nodes (LN) is CD1c+, CD1a-, and CD1b- prompted us to further investigate the expression of these molecules on normal, activated, and malignant B cells. We report that blood and spleen contain CD1c+ B cells that account for 49% +/- 20.4% (mean +/- SD) and 50.9% +/- 4.4% of the total B cell population, respectively. CD1a- and CD1b-specific MoAbs are unreactive with both B and T cells; these latter are CD1c- as well. When CD1c+ and CD1c- B cells are activated in vitro, the CD1c molecule is upregulated in the former subset and induced de novo in the latter. Conversely, activated blood T cells remain CD1c-. Neither CD1a nor CD1b molecules are detected on activated T and B lymphocytes. At ultrastructural level, the CD1c+ B cells exhibit distinctive features, namely, condensed chromatin with or without a nucleolus and a unique cluster of cytoplasmic vesicles and organelles; the number of nucleolated cells is higher in the spleen (95%) than in the tonsil (40%) or blood (5%). These findings further confirm the similarity between blood and MZ B cells. The CD1c expression assessed on 27 B-cell chronic lymphocytic leukemias (B-CLL) and 46 B non-Hodgkin's lymphomas (B-NHL) was detected on 41% and 32% of cases, respectively; the latter comprised four follicular and 11 diffuse histotypes. The Burkitt's lymphomas were CD1c-negative. The B-cell neoplasms were all CD1a- and, except for four with a weak cytoplasmic staining, all CD1b- as well. The clear-cut CD1c distribution in normal LN (MZ+, GC-) contrasted with the evidence that some B-NHL cells of GC origin (eg, follicular with predominantly small cleaved cells) were CD1c+. Overall, the finding that CD1c expression is restricted to a fraction of B cells present in lymphoid organs and in peripheral blood indicates that CD1c is a powerful marker for the identification and dissection of B-cell subsets whose functional properties can now be evaluated.

Modulation of acute graft-versus-host disease and chimerism after adoptive transfer of in vitro-expanded invariant Vα14 natural killer T cells

2006 ◽  
Vol 106 (1) ◽  
pp. 82-90 ◽  
Author(s):  
Masaki Kuwatani ◽  
Yoshinori Ikarashi ◽  
Akira Iizuka ◽  
Chihiro Kawakami ◽  
Gary Quinn ◽  
...  
Keyword(s):  
T Cells ◽  
Natural Killer ◽  
Graft Versus Host Disease ◽  
Adoptive Transfer ◽  
Natural Killer T Cells ◽  
Host Disease ◽  
Graft Versus Host ◽  
Killer T Cells ◽  
Acute Graft

scholarly journals T-suppressor cells sensitive to cyclophosphamide and to its in vitro active derivative 4-hydroperoxycyclophosphamide control the mitogenic response of murine splenic B cells to dextran sulfate. A direct proof for different sensitivities of lymphocyte subsets to cyclophosphamide

1979 ◽  
Vol 150 (6) ◽  
pp. 1571-1576 ◽  
Author(s):  
T Diamantstein ◽  
E Willinger ◽  
J Reiman
Keyword(s):  
T Cells ◽  
Dextran Sulfate ◽  
Cell Subset ◽  
Direct Proof ◽  
Suppressor Cells ◽  
Thymidine Uptake ◽  
Spleen Cells ◽  
Active Derivative ◽  
T Suppressor Cells

As measured by [(3)H]thymidine uptake, spleen cells of mice injected 7 d previously with a single dose of cyclophosphamide (Cy) (125 mg x kg (-1)) gave an enhanced response to dextran sulfate (DS), a diminished response to lipopolysaccharide (LPS), and a normal response to concanavalin A. Addition of syngeneic thymocytes to spleen cells inhibited the enhanced response of the cells to DS and slightly enhanced their response to LPS. Pretreatment of thymocytes by 4-hydroxyperoxycyclophosphamide (4HP-Cy) in vitro (an in vitro active derivative of Cy) abrogated the effect of thymocytes on the DS response but not on the LPS response. Pretreatment of spleen cells by small doses of 4HP-Cy (0.1-1.0 μg. ml(-1)) in vitro enhanced the capacity of the cells to respond to DS but either did not affect, or even diminished their capacity to respond to LPS. The enhancement of the DS response by 4HP-Cy treatment could not be detected using spleen cells depleted of T cells or lacking functioning T cells. 4HP-Cy doses more than 3 μg ml(-1) diminished or abolished the capacity of the spleen cells to respond to LPS as well as their capacity to respond to DS. The results show (a) that in contrast to the LPS-reactive B-lymphocyte subset, the proliferative capacity of DS-reactive subset is negatively controlled by a Cy- and 4HP-Cy-sensitive T-cell subset and (b) that these T- suppressor cells are more sensitive to Cy and 4HP-Cy (to their respective active alkylating metabolites) than B lymphocytes and T cells carrying other immunological functions.

scholarly journals Elimination of syngeneic sarcomas in rats by a subset of T lymphocytes.

1980 ◽  
Vol 152 (4) ◽  
pp. 823-841 ◽  
Author(s):  
E Fernandez-Cruz ◽  
B A Woda ◽  
J D Feldman
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Cell Subset ◽  
Suppressor Cells ◽  
Effector Cells ◽  
Long Duration ◽  
Ia Antigens

Established subcutaneous Moloney sarcomas (MST-1) of large size and long duration were eliminated from syngeneic rats by intravenous infusion of varying numbers of specific syngeneic effector T lymphocytes. Spleen cells from BN rats in which tumor had regressed were cultured in an in vitro mixed lymphocyte tumor cell culture (MLTC) to augment cytotoxicity of effector cells. In the MLTC a T cell subset was expanded in response to MST-1 antigens and transformed into blast elements. With these changes, there was an increase in the W3/25 antigen on the T cell surface, a decrease of W3/13 antigen, and an increase in the number of T cells with Ia antigens. The subset associated with elimination of established tumors was a blast T cell W3/25+, W3/13+, as detected by monoclonal antibodies to rat T antigens. The W3/25+ subset was poorly cytotoxic in vitro for MST-1 and apparently functioned in vivo as an amplifier or helper cell in the tumor-bearing host. The W3/25- population was a melange of cells that included (W3/13+, W3/25-) T cells, null cells, Ig+ cells, and macrophages, and was associated with enhancement of tumor in vivo, suggesting the presence of suppressor cells.

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