scholarly journals LAK cells prevent lethal graft-versus-host disease: Use of LAK cells as veto and natural suppressor cells.

1990 ◽  
Vol 13 (1) ◽  
pp. 38-42
Author(s):  
Eiichi Azuma ◽  
Yoshihiro Komada ◽  
Minoru Sakurai
Keyword(s):  
Graft Versus Host Disease ◽  
Suppressor Cells ◽  
Lak Cells ◽  
Host Disease ◽  
Graft Versus Host ◽  
Natural Suppressor Cells

scholarly journals Mechanism of Suppression Effect of Myeloid-Derived Suppressor Cells on Hyperacute Graft-Versus-Host Disease

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5716-5716
Author(s):  
Yigeng Cao ◽  
Ming-Zhe Han ◽  
Peng Liu ◽  
Haiyan Gong ◽  
Haiyan Zhu ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Graft Versus Host Disease ◽  
Suppressor Cells ◽  
Cd8 T Cell ◽  
Large Sample Size ◽  
Myeloid Derived Suppressor Cells ◽  
Common Complication ◽  
Host Disease ◽  
Graft Versus Host

Abstract Allogeneic HSCT (allo-HSCT) is associated with serious side effects and its most common complication is graft-versus-host disease (GVHD). Hyperacute GVHD is a clinical syndrome that occurs within the first 14 days after allo-HSCT associated with significant morbidity and mortality. The large sample size of clinical study indicated that the incidence of hyperacute GVHD in patient who underwent an allo-HSCT was about 9%, but the pathological process and crucial factor of this complication have incompletely defined. Myeloid-derived suppressor cells (MDSCs) have been found that had a beneficial role in treatment of GVHD, on account of suppressing ability on alloreactive T-cell-response in vitro and in vivo. It was reported that reactive oxygen species (ROS) have been implicated in MDSCs-mediated T cell suppression and MDSCs from NOX2-deficient mice, chronic granulomatous disease (CGD) mice, failed to suppress T cell function. However, the investigation of whether and how MDSCs and ROS play in CGD mice receiving allo-HSCT is lacking. In our research, WT mice receiving allo-HSCT began to appear typical acute GVHD clinical manifestations in about 20 days and died within 30 days after transplantation, while CGD mice receiving allo-HSCT suddenly suffered from hyperacute GVHD at day 3 after allo-HSCT: performed continuous weight loss, demonstrated poor grooming and impairs movement with or without hunching or skin integrated and animals died within 2 days after onset of symptoms. Further study shown that the donor spleen derived T cells was indispensable for hyperacute GVHD of CGD mice after receiving allo-HSCT. T lymphocyte subsets and proportional change in bone marrow and spleen of each group were detected by flow cytommeter after transplantation. The percentage and absolute number of donor derived CD3+CD8+T cell from both BM and spleen of CGD were significant higher than that of WT mice received allo-HSCT. Moreover, cell size and expression of activation marker CD25, CD44, and CD69 of CD3+CD8+T cell from both BM and spleen of CGD mice were significant higher than that of WT mice. The killing ability of donor derived CD3+T cells was observed by the living cells workstation and it was obviously to see that allo-reactive T cells from CGD mice had stronger killing ability. The levels of different cytokines in serum of recipient mice were detected by protein chip at day 3 after allo-HSCT. Comparing to C57BL/6 mice, more than ten kinds of inflammatory factors, including IL-6, were increased in the serum of CGD mice, which indicated that the cytokine storm related to T cells might be occur during hyperacute GVHD. In addition, using this hyperacute mouse model, we revealed that application of ROS agonist, L-buthionine-S, R-sulfoximine (BSO), rescued the CGD mice receiving allo-HSCT from hyperacute GVHD. In General, this study pioneering established a stable murine model of hyperacute GVHD and proved that allo-reactive T cells massively activated and proliferated since ROS production defective MDSCs lose the ability of inhibiting T cell immune reaction and caused hyperacute GVHD. These data provided new insights into the pathogenesis of GVHD and may improve the clinical management of this common complication. Disclosures No relevant conflicts of interest to declare.

scholarly journals CD99-dependent expansion of myeloid-derived suppressor cells and attenuation of graft-versus-host disease

2012 ◽  
Vol 33 (3) ◽  
pp. 259-267 ◽  
Author(s):  
Hyo Jin Park ◽  
Dahye Byun ◽  
An Hi Lee ◽  
Ju Hyun Kim ◽  
Young Larn Ban ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Host Disease ◽  
Graft Versus Host

scholarly journals The Role of Myeloid-Derived Suppressor Cells (MDSCs) in Graft-versus-Host Disease (GVHD)

2021 ◽  
Vol 10 (10) ◽  
pp. 2050
Author(s):  
Christos Demosthenous ◽  
Ioanna Sakellari ◽  
Vassiliki Douka ◽  
Penelope Georgia Papayanni ◽  
Achilles Anagnostopoulos ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Suppressor Cells ◽  
Hematologic Malignancies ◽  
In Vivo Studies ◽  
Myeloid Derived Suppressor Cells ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Published Evidence

Background: Myeloid-derived suppressor cells (MDSCs) are implicated in the complex interplay involving graft-versus-leukemia (GVL) effects and graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HCT) in hematologic malignancies. Methods: A review of literature through PubMed was undertaken to summarize the published evidence on the pathophysiology and clinical implications of MDSCs in allo-HCT. Literature sources published in English since 1978 were searched, using the terms Natural Suppressor (NS) cells, MDSCs, GVHD, and allo-HCT. Results: In vivo studies demonstrated that MDSCs derived from mobilization protocols could strongly suppress allo-responses mediated by T cells and enhance T-Reg activity, thus inhibiting GVHD toxicity. However, the influence of MDSCs on the GVL effect is not fully defined. Conclusions: The induction or maintenance of MDSC suppressive function would be advantageous in suppressing inflammation associated with GVHD. Pathways involved in MDSC metabolism and the inflammasome signaling are a promising field of study to elucidate the function of MDSCs in the pathogenesis of GVHD and translate these findings to a clinical setting.

scholarly journals Human lymphokine activated killer (LAK) cells suppress generation of allospecific cytotoxic T cells: implications for use of LAK cells to prevent graft-versus-host disease in allogeneic bone marrow transplantation

Blood ◽  
1992 ◽  
Vol 79 (1) ◽  
pp. 261-268
Author(s):  
J Uberti ◽  
F Martilotti ◽  
TH Chou ◽  
J Kaplan
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Graft Versus Host Disease ◽  
Cytotoxic T Cells ◽  
Allogeneic Bone Marrow Transplantation ◽  
Lak Cells ◽  
Allogeneic Bone ◽  
Host Disease ◽  
Graft Versus Host ◽  
Lak Cell

We have found that murine lymphokine activated killer (LAK) cells have veto and natural suppressor activities in vitro, and prevent graft- versus-host disease (GVHD) in vivo. To determine whether human LAK cells mediate veto and natural suppression we measured their ability to inhibit generation of allospecific cytotoxic T cells (CTL) in mixed lymphocyte culture (MLC). When added to MLCs at low concentrations LAK cells caused veto-type inhibition: stimulator-type LAK cells inhibited generation of CTL but responder or third-party LAK cells did not. At higher concentrations LAK cells caused nonspecific inhibition: all three LAK cell types inhibited generation of CTL. LAK cell veto and natural suppressor activities were largely eliminated by irradiation with 30 Gy and by depletion of CD56+ cells, but increased after depletion of CD3+ cells. LAK cell veto activity is not likely an artifact of cold-target inhibition by the LAK cells themselves or by proliferation of T cells contaminating LAK cell preparations: (1) veto only occurred when LAK cells were added to MLC on days 0 through 2, but not when added on day 5; (2) addition of saturating numbers of labeled targets to fixed numbers of allo-CTL effectors failed to overcome the inhibitory effects of adding stimulator-type LAK cells at the onset of MLC; and (3) CD3-depleted LAK cells showed greater veto activity than threefold greater numbers of control LAK cells. In light of our previous findings in mice, the current results imply that adoptive immunotherapy with LAK cells may be useful in preventing GVHD in human bone marrow transplant recipients.

scholarly journals Allogeneic Hematopoietic Stem Cell Transplantation Mobilized With Pegylated Granulocyte Colony-Stimulating Factor Ameliorates Severe Acute Graft-Versus-Host Disease Through Enrichment of Monocytic Myeloid-Derived Suppressor Cells in the Graft: A Real World Experience

2021 ◽  
Vol 12 ◽  
Author(s):  
Lin Li ◽  
Jin Yin ◽  
Yun Li ◽  
Chunyan Wang ◽  
Xia Mao ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Acute Graft

We compared the effectiveness and safety of pegylated granulocyte colony-stimulating factor (peg-G-CSF) vs. non-peg-G-CSF for hematopoietic stem cell mobilization in allogeneic hematopoietic stem cell transplantation in a real-world setting. We included 136 consecutive healthy donors treated with non–peg-G-CSF (n = 53) or peg-G-CSF (n = 83), and 125 consecutive recipients (n = 42 and 83, respectively) in this study. All harvesting was completed successfully. No significant difference in leukapheresis number and adverse events frequency was observed, nor were there severe adverse events leading to discontinuation of mobilization. The leukapheresis products mobilized by peg-G-CSF had higher total nucleated cells (p < 0.001), monocytic myeloid-derived suppressor cells (p < 0.001), granulocytic myeloid-derived suppressor cells (p = 0.004) and B cells (p = 0.019). CD34+ cells and other lymphocyte subsets (T cells, regulatory T cells, natural killer [NK] cells, etc.) were similar in both apheresis products. Patients who received grafts mobilized by peg-G-CSF exhibited a lower incidence of grade III-IV acute graft-versus-host disease (p = 0.001). The 1-year cumulative incidence of chronic graft-versus-host disease and relapse, 1-year probability of graft-versus-host disease-free relapse-free survival, and overall survival did not differ significantly between subgroups. Our results suggest that collecting allogeneic stem cells after the administration of peg-G-CSF is feasible and safe. Peg-G-CSF mobilized grafts may reduce severe acute graft-versus-host disease compared with non-peg-G-CSF mobilized grafts after allogeneic stem cell transplantation. The beneficial effects of a peg-G-CSF graft might be mediated by increased numbers of monocytic myeloid-derived suppressor cells.

scholarly journals Analysis of late infections after human bone marrow transplantation: role of genotypic nonidentity between marrow donor and recipient and of nonspecific suppressor cells in patients with chronic graft-versus-host disease

Blood ◽  
1982 ◽  
Vol 60 (3) ◽  
pp. 714-720 ◽  
Author(s):  
K Atkinson ◽  
V Farewell ◽  
R Storb ◽  
MS Tsoi ◽  
KM Sullivan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Hematologic Malignancy ◽  
Chronic Gvhd ◽  
Suppressor Cells ◽  
Host Disease ◽  
Varicella Zoster ◽  
Graft Versus Host

Infections occurring 6 mo or later after bone marrow transplantation for severe aplastic anemia or hematologic malignancy were analyzed in 98 long-term survivors. Varicella-zoster (VZ) infections were analyzed separately from all other infections. The factor predisposing most strongly to late VZ infection was genotypic nonidentity for HLA between marrow donor and recipient. There was a suggestion that chronic graft- versus-host disease (GVHD) associated with the presence of nonspecific suppressor cells also predisposed to late VZ infection, while age less than 10 yr was protective against such infections. Chronic GVHD predisposed to late non-VZ infections, but this was not increased by the presence of nonspecific suppressor cells. HLA nonidentify between patient and marrow donor further increased the risk of late non-VZ infections over and above that due to the presence of chronic GVHD. Receipt of a syngeneic transplant appeared protective for late non-VZ infections. These findings suggest that full genotypic identity for HLA between donor and recipient may be required for optimal immune reconstitution after marrow transplantation and may denote a possible biologic role for nonspecific suppressor T cells in humans.

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