Reconstitution of Regulatory T Cells Involves in the Development of Acute Graft-Versus-Host Disease after Hematopoietic Stem Cell Transplantation.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2204-2204
Author(s):  
Shuhei Karakawa ◽  
Kazuhiro Nakamura ◽  
Keiichi Hara ◽  
Yoko Mizoguchi ◽  
Mizuka Miki ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Regulatory T Cells ◽  
Cd4 T Cells ◽  
Acute Gvhd ◽  
The Other ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Self Tolerance

Abstract Graft-versus-host disease (GVHD) is a significant complication in hematopoietic stem cell transplantation (SCT). On the other hand, graft-versus-tumor (GVT) effect has been known to be concerned with the prevention of relapses in various hematological or non-hematological malignant disorders. The regulation of GVHD without suppressing GVT effect is a pivotal role in the success of hematopoietic SCT. Recently CD4+CD25+regulatory T cells have been recognized to regulate the maintenance of self-tolerance, and associate with several autoimmune diseases. In transplant immunity, CD4+CD25+regulatory T cells have been reported to regulate GVHD without suppressing GVT effect in several animal studies. Natural killer T (NKT) like cells also have been recognized to associated with the maintenance of self-tolerance by inducing CD4+CD25+regulatory T cells through the production of IL-2. In this study, we examined the roles of CD4+CD25+regulatory T cells and NKT like cells in cases underwent hematopoietic SCT. Blood samples from patients underwent SCT in our institution during past 3 years (7 months through 26 years of age, n =19) were obtained every two weeks until day 90 after SCT. Primary disorders of patients were non-malignant hematological disease such as aplastic anemia (n=3), chronic granulomatous disease (n=8) and malignant disease such as leukemia (n=5), and solid tumors (n=3). Pre-conditioning regimens used in this study were myeloablative regimens in 10 cases and reduced intensity regimens in 9 cases, respectively. The frequencies of CD4+CD25+regulatory T cells were assessed by the expression of CD4 and CD25, and those of NKT like cells were assessed by the expression of CD3, CD16, and CD56 using flow cytometry. The mRNA expression of FOXP3 in purified CD4+CD25+regulatory T cells were determined by quantitative real-time PCR method. In 13 patients who had none or Grade 1 acute GVHD, the frequency of CD4+CD25+regulatory T cells in CD4+ T cells was increased up to 25–90% at early period after SCT and normalized below 20% after day 45 post SCT. On the other hand, four of 6 patients who had acute GVHD (more than Grade 2) showed that the frequency of CD4+CD25+regulatory T cells in CD4+ T cells persisted below 20%. In other one patient, the development of acute GVHD (Grade 2) was associated with decreasing the frequency of CD4+CD25+regulatory T cells (30 to 10%) and the recovery of GVHD was found with increasing CD4+CD25+regulatory T cells (10 to 30%). The mean frequency of CD4+CD25+regulatory T cells in CD4+ T cells on day 15 after SCT was 44% in patients without GVHD and 21% in patients with GVHD (p=0.07). No difference in the expressions of FOXP3 mRNA in purified CD4+CD25+regulatory T cells was noted between patients with GVHD and those without GVHD. The reconstitution pattern of CD3+CD16+CD56+ NKT like cells after SCT was not associated with the development of GVHD. These results suggest that the development of acute GVHD may be strongly associated with the reconstitution of donor derived CD4+CD25+regulatory T cells in CD4+ T cells. The measurement of CD4+CD25+regulatory T cells in CD4+ T cells might lead to the early diagnosis and the prevention of acute GVHD. (Future studies will be needed to examine the association between the frequency of regulatory T cells and GVT effect.)

scholarly journals Prior Use of Mogamulizumab to Allogenic Hematopoietic Stem Cell Transplantation Induces Severe Acute Graft-Versus-Host Disease

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1940-1940 ◽  
Author(s):  
Takeshi Sugio ◽  
Koji Kato ◽  
Takatoshi Aoki ◽  
Takanori Ota ◽  
Noriyuki Saito ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Regulatory T Cells ◽  
Research Funding ◽  
Acute Gvhd ◽  
Cell Lymphoma ◽  
Hematopoietic Stem ◽  
Graft Versus Host

Abstract [Introduction] Adult T-cell leukemia/lymphoma (ATL) is an aggressive peripheral T-cell lymphoma (PTCL) with a dismal prognosis. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative treatment in ATL patients. Mogamulizumab, a humanized anti-CC chemokine receptor 4 (CCR4) monoclonal antibody, is a novel immunotherapeutic agent, effective in treating patients with PTCL such as ATL, PTCL-not specified, and cutaneous T-cell lymphoma. However, in allo-HSCT setting, we should be careful to use mogamulizumab because CCR4 is expressed in regulatory T cells: The mogamulizumab treatment may accelerate GVHD by eradicating regulatory T cells in allo-HSCT patients. Here, we retrospectively analyzed the effect of mogamulizumab on GVHD development in ATL patients treated with mogamulizumab prior to allo-HSCT. [Patients and Methods] Data from the Fukuoka Bone Marrow Transplantation Group were retrospectively analyzed after the approval of mogamulizumab use in Japan. [Results] A total of 24 patients with ATL received mogamulizumab prior to allo-HSCT between April 2012 and April 2015 in our group. The median age at allo-HSCT was 58.5 years (range, 32-72). The median intervals from the last administration of mogamulizumab to allo-HSCT were 25 days (range, 9-126). The median total dose of mogamulizumab was 3 mg/kg (range, 1-8 mg/kg). After treatment with mogamulizumab, 18 patients (75%) had achieved in remission (CR in 4 patients and PR in 14) at allo-HSCT. Ten patients received unrelated bone marrow, 5 received related peripheral blood, and 9 received cord blood as stem cell sources. Eleven patients were treated with full-intensity conditioning and 13 received reduced-intensity conditioning. Graft-versus-host disease (GVHD) prophylaxis consisted of calcineurin inhibitors (cyclosporine or tacrolimus) with short-term methotrexate in 14 patients and mycophenolate mofetil in 9. The cumulative incidence (CI) of acute GVHD at 100 days was 66.6% in grade 2-4 and 33.3% in grade 3-4. The involved organs of acute GVHD were skin in 14 patients, gut in 10, and liver in 4. Among 14 patients who developed grade 2-4 acute GVHD, 5 had severe fluid retention such as pleural effusion or ascites associated with GVHD. Chronic GVHD was observed in 6 patients, and 5 of them were extensive disease. The CI of transplant-related mortality (TRM) and relapse at 1-year were 53.2% (95%CI, 29.3-72.3%) and 29.6% (95%CI, 12.6-48.9%), respectively. The leading cause of death was GVHD (n = 7). The 1-year overall survival and progression-free survival were 19.2% (95%CI, 5.7-38.8%) and 17.2% (95%CI, 4.9-35.7%), respectively. [Discussion] Use of mogamulizumab prior to transplantation in allo-HSCT patients has a merit to decrease the burden of ATL cells. However, it was associated with an increase of TRM due to severe GVHD. Although most of ATL patients achieved better disease status at allo-HSCT through mogamulizumab and the survival rate was expected to be 50% based on the previous data, the survival in the present study was ~20%. These data suggest that mogamulizumab administered before transplantation may have retained until an early phase of post-transplantation, and the donor or host-derived regulatory T cells might be eliminated, allowing the GVHD T-cell clone to expand. Since mogalizumab is a potent anti-ATL agent, we need to develop new treatment protocols integrating mogalizumab at a suitable dose or administration timing, to minimize the unwanted GVHD development in future studies. Disclosures Akashi: Asahi Kasei: Research Funding, Speakers Bureau; Shionogi: Research Funding, Speakers Bureau; Astellas: Research Funding, Speakers Bureau; Celgene: Research Funding, Speakers Bureau; Chugai: Research Funding, Speakers Bureau; Bristol-Myers Squibb: Research Funding, Speakers Bureau; Novartis Pharma K.K.: Consultancy, Research Funding, Speakers Bureau; Kyowa Hakko Kirin Co., Ltd.: Consultancy, Research Funding, Speakers Bureau.

scholarly journals mTEC damage risks immune recovery

2021 ◽  
Vol 219 (2) ◽  
Author(s):  
Yousuke Takahama
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Immune Recovery ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Self Tolerance ◽  
Medullary Epithelial Cells

Whether autologous hematopoietic stem cell transplantation is free from graft-versus-host disease is controversial. Alawam et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20211239) now demonstrate that prolonged damage in thymic medullary epithelial cells causes the failure in self-tolerance in newly generated T cells and provokes post-transplant autoimmunity.

Separating graft-versus-leukemia from graft-versus-host disease in allogeneic hematopoietic stem cell transplantation

Immunotherapy ◽  
2009 ◽  
Vol 1 (4) ◽  
pp. 599-621
Author(s):  
Jian-Ming Li ◽  
Cynthia R Giver ◽  
Ying Lu ◽  
Mohammad S Hossain ◽  
Mojtaba Akhtari ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Graft Versus Leukemia

Routine methods to maximize the graft-versus-leukemia (GvL) activity of allogeneic hematopoietic stem cell transplantation (HSCT) without the detrimental effects of graft-versus-host disease (GvHD) are lacking. Depletion or inhibition of alloreactive T cells is partially effective in preventing GvHD, but usually leads to decreased GvL activity. The current model for the pathophysiology of acute GvHD describes a series of immune pathways that lead to activation of donor T cells and inflammatory cytokines responsible for tissue damage in acute GvHD. This model does not account for how allotransplant can lead to GvL effects without GvHD, or how the initial activation of donor immune cells may lead to counter-regulatory effects that limit GvHD. In this review, we will summarize new findings that support a more complex model for the initiation of GvHD and GvL activities in allogeneic HSCT, and discuss the potential of novel strategies to enhance GvL activity of the transplant.

Increased Effector CD4+ T-Cells Early Post Hematopoietic Stem Cell Transplantation Using an Alemtuzumab-Based Reduced Intensity Conditioning Regimen Correlate with Subsequent Development of Graft Versus Host Disease.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4999-4999
Author(s):  
Katie Matthews ◽  
ZiYi Lim ◽  
Laurence Pearce ◽  
Khalid Tobal ◽  
Alejandro Madrigal ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Cd4 T Cells ◽  
Subsequent Development ◽  
Effector T Cells ◽  
Cd4 T Cell ◽  
Hematopoietic Stem ◽  
Graft Versus Host

Abstract Lymphocyte depletion using the anti CD52 monoclonal antibody alemtuzumab reduces the incidence of graft versus host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), but some patients still develop this potentially life-threatening complication. We previously reported that patients achieving rapid full donor T cell chimerism after fludarabine, busulphan and alemtuzumab (FBC) conditioned allo-HSCT have a significantly increased risk of GvHD compared to patients with prolonged mixed donor chimerism beyond day 100 (Lim et al. Br. J. Haematology 2007). We performed a prospective study of 29 patients who received allo-HSCT with FBC conditioning (median age: 53 years; range: 34 – 69 presenting with AML or MDS) to examine the kinetics of lymphocyte reconstitution in relation to T-cell chimerism patterns and incidence of GvHD. Naïve, memory, effector and terminally differentiated CD4+ and CD8+ T-cells, activated T-cells (CD25+ HLA-DR+); putative regulatory CD4+ CD25high Foxp3+ T-cells, B-cells and NK cells were enumerated in whole peripheral blood of patients at days 30, 60, 90, 180, 270 and 360 after HSCT. Chimerism analysis of purified T-cells was performed by genetic profiling of polymorphic short tandem repeat loci. Ten patients developed GvHD (acute or chronic). Although alemtuzumab induced profound depletion of all T-cell subsets, significantly higher numbers of CD4+ effector (CD45RO+ CD27−) T-cells were detected at day 30 post transplant in patients who later developed GvHD (24 cells/μl; range: 1 – 84 cells/μl) compared to patients without GvHD (5 cells/μl; range: 1 – 40 cells/μl) (p = 0.026). In contrast, there were no significant differences in the numbers or rate of reconstitution of CD8+ T-cell sub-populations, NK cells or B-cells in patients that developed GvHD and those who did not at any time points. T-cells present at day 30 in patients that subsequently developed GvHD were 100% donor whereas the majority of patients that did not develop GvHD exhibited mixed donor and recipient T cell chimerism. Development of GvHD pathology was associated with expansion of these donor effector CD4+ T-cells (at day 60: 35 cells/μl; range: 9 – 154 cells/μl compared to 7 cells/μl; range: 1 – 56 cells/μl for patients without GvHD, p = 0.04). Absolute numbers of CD4+ CD25high Foxp3+ T-cells at day 30 were similar in both groups of patients (p = 0.8). However, of note, a significant deficit of these putative regulatory T-cells in the group that developed GvHD was apparent when numbers were considered relative to CD4+ effector T cells at day 30 (41 CD4+ effector T-cells; range: 28 – 51 /per regulatory CD4+ T cell for the GvHD group compared to 12 CD4+ effector T-cells; range: 2 – 33 /per regulatory CD4+ T-cell for patients without GvHD, p = 0.03). We speculate the higher numbers of effector CD4+ T-cells detected in patients at day 30 post HSCT are donor-derived mature T cells that alemtuzumab fails to deplete. In the solid organ transplant setting, alemtuzumab has been shown to be relatively sparing of effector memory CD4+ T-cells. Our correlation of donor-derived effector CD4+ T-cells with subsequent development of GvHD suggests they are alloreactive and that a deficit of T-regs relative to CD4+ effector T-cells early post HSCT contributes to GvHD.

Role of Il-17 Varies at Different Periods After Hematopoietic Stem Cell Transplantation: Protection From Acute Graft-Versus-Host Disease and Exacerbation of Chronic Graft-Versus-Host Disease.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3741-3741 ◽  
Author(s):  
Rie Kuroda ◽  
Ryosei Nishimura ◽  
Katsuaki Sato ◽  
Hideaki Maeba ◽  
Kazuhito Naka ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Immune Cells ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
Graft Versus Host

Abstract Abstract 3741 Th17 is a newly identified T cell lineage that secretes the proinflammatory cytokine IL-17. Th17 cells have been shown to play a crucial role in mediating autoimmune diseases such as experimental autoimmune encephalomyelitis (EAE), arthritis, and colitis. Anti-IL-17 therapy for some autoimmune diseases in clinical settings has been started and promising results have been reported. However the role of IL-17 on developing acute and chronic GVHD in hematopoietic stem cell transplantation (HSCT) is not yet fully understood. Interaction between IL-17 and IL-17 receptor is complicated because IL-17 is produced in various kinds of immune cells other than CD4+ T-cells, and IL-17 receptors express on not only immune cells but also various epithelial cells, including lung and intestine, both of which are target organs of GVHD. To explore the role of host derived or donor derived IL-17 separately in acute GVHD, lethally irradiated wild type (WT) or IL-17 knockout (KO) Balb/c (H-2d) were given WT or IL-17 KO C57BL/6 (H-2b) bone marrow (BM) cells with WT splenocytes to induce acute GVHD. Infused cell number of WT splenocytes in this study induced acute GVHD, but not lethal in IL-17 WT host mice. In contrast, IL-17 KO host mice receiving WT BM plus WT splenocytes developed severe acute gut GVHD and finally half of them died (p<0.05). To exclude the possibility that alloreactivity of host IL-17 KO derived dentritic cells (DCs) could be much more than that of WT DCs, mixed leukocyte reaction (MLR) was performed using stimulators from WT or IL-17 KO DCs and responders from WT CD4+ T-cells. No significant differences were observed between WT DCs and IL-17 KO DCs in thymidine uptake and percentage of responder cells producing IFN-g or TNF-a. Taken together, host-derived IL-17 has a protective effect against acute GVHD. Moreover similar results were observed when IL-17 KO Balb/c mice were given BM cells from another strain B10.D2 plus splenocytes shown in the figure below (p<0.05). Next, we compared the development of chronic GVHD between the lethally irradiated WT Balb/c mice given IL-17 KO C57BL/6 BM cells or WT BM cells with low dose WT splenocytes to induce sublethal acute GVHD and chronic GVHD subsequently. After day 60 the mice receiving WT BM cells plus WT splenocytes experienced weight loss accompanied by skin histological changes (p<0.05, shown in the figure below), while mice receiving IL-17 KO BM plus WT splenocytes showed minimal signs of GVHD as well as mice receiving IL-17 KO BM or WT BM alone. Increased number of donor-BM derived IL-17 producing cells was observed in the mice showing chronic GVHD compared to BM control (p<0.05). Moreover, a significant increase of T-cell proliferation was observed by adding rIL-17 into MLR culture (p<0.05). These results suggest that donor BM derived IL-17 producing cells involved in the pathogenesis of chronic GVHD by exacerbating the alloimmune response in part. In conclusion IL-17, especially from host-derived, has a protective effect against acute GVHD. On the contrary, donor BM derived IL-17 exacerbates chronic GVHD. Neutralizing IL-17 would be a potent strategy only for preventing chronic GVHD, not for acute GVHD. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Phosphorylated ERK1/2 in CD4 T cells is associated with acute GVHD in allogeneic hematopoietic stem cell transplantation

2020 ◽  
Vol 4 (4) ◽  
pp. 667-671
Author(s):  
Hidekazu Itamura ◽  
Takero Shindo ◽  
Satoshi Yoshioka ◽  
Takayuki Ishikawa ◽  
Shinya Kimura
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Acute Gvhd ◽  
Hematopoietic Stem

Abstract To diagnose graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is sometimes difficult. We showed previously that MEK inhibitors selectively suppress murine GVHD while retaining antiviral and antitumor immunity. Here, we asked whether the RAS/MEK/ERK pathway is activated in human allo-HSCT recipients with GVHD, and whether the phosphorylated ERK1/2 can be a biomarker of GVHD. Peripheral blood was sequentially collected from 20 allo-HSCT recipients: 1 bone marrow transplant, 7 peripheral blood stem cell transplants (PBSCT), and 12 cord blood transplants. Ten of the 20 allo-HSCT recipients developed GVHD, and phosphorylation of ERK1/2 in T and B cells was analyzed by flow cytometry. Occurrence of acute GVHD was associated with phosphorylation of ERK1/2 in CD4+ T cells at day 30 (P &lt; .001), which was suppressed by ex vivo exposure to a MEK inhibitor trametinib at clinically achievable concentrations. In particular, ERK1/2 was phosphorylated preferentially in naive/central memory CD4+ T cells. Notably, phosphorylation of ERK1/2 fell as GVHD improved. These results suggest that phosphorylation status of ERK1/2 in peripheral blood CD4+ T cells may be a future biomarker for diagnosing human GVHD, and the potential efficacy of MEK inhibitors against human GVHD.

scholarly journals Reduced frequency of FOXP3+ CD4+CD25+ regulatory T cells in patients with chronic graft-versus-host disease

Blood ◽  
2005 ◽  
Vol 106 (8) ◽  
pp. 2903-2911 ◽  
Author(s):  
Emmanuel Zorn ◽  
Haesook T. Kim ◽  
Stephanie J. Lee ◽  
Blair H. Floyd ◽  
Despina Litsa ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Regulatory T Cells ◽  
Stem Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Healthy Individuals ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Healthy Donors

AbstractChronic graft-versus-host disease (cGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation but the immune mechanisms leading to the diverse clinical manifestations of cGVHD remain unknown. In this study, we examined regulatory T cells (Tregs) in 57 transplant recipients (30 with cGVHD and 27 without active cGVHD) and 26 healthy donors. Phenotypic studies demonstrated decreased frequency of CD4+CD25+ T cells in patients with cGVHD compared with patients without cGVHD (P &lt; .001) and healthy individuals (P &lt; .001). Gene expression of Treg transcription factor FOXP3 was reduced in cGVHD patients compared with patients without cGVHD (P = .009) or healthy donors (P = .01). T-cell receptor excision circle (TREC) assays for the evaluation of thymus activity revealed fewer TRECs in both transplant groups compared with healthy donors (P &lt; .001 and P = .02, respectively) although no difference was observed between patients with or without cGVHD (P = .13). When tested in functional assays, Tregs from both patient cohorts and healthy individuals mediated equivalent levels of suppression. Collectively, these studies indicate that patients with active cGVHD have reduced frequencies of Tregs but the function of these cells remains normal. These findings support the development of new strategies to increase the number of Tregs following allogeneic hematopoietic stem cell transplantation to prevent or correct cGVHD. (Blood. 2005; 106:2903-2911)

scholarly journals Donor Cell Composition and Reactivity Predict Risk of Acute Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Darius Sairafi ◽  
Arwen Stikvoort ◽  
Jens Gertow ◽  
Jonas Mattsson ◽  
Michael Uhlin
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Hematopoietic Stem ◽  
Graft Versus Host

Background. Graft-versus-host disease (GVHD) is a serious complication after allogeneic hematopoietic stem cell transplantation (HSCT). We designed a functional assay for assessment of individual risk for acute GVHD.Study Design and Methods. Blood samples were collected from patients and donors before HSCT. Two groups of seven patients each were selected, one in which individuals developed acute GVHD grades II–IV and one in which none showed any clinical signs of GVHD. Peripheral blood mononuclear cells (PBMCs) isolated from donors were incubated in mixed lymphocyte cultures (MLCs) with recipient PBMCs. The cells were characterized by flow cytometry before and after MLC.Results. Samples from donors in the GVHD group contained significantly lower frequencies of naïveγδT-cells and T-cells expressing NK-cell markers CD56 and CD94. Donor samples in this group also exhibited lower frequencies of naïve CD95+T-cells compared to controls. After MLC, there were dissimilarities in the CD4/CD8 T-cell ratio and frequency of CD69+T-cells between the two patient groups, with the non-GVHD group showing higher frequencies of CD8+and CD69+T-cells.Conclusion. We conclude that a thorough flow cytometric analysis of donor cells for phenotype and allogeneic reactivity may be of value when assessing pretransplant risk for severe acute GVHD.

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