Recovery of Varicella-Zoster Virus–Specific T Cell Immunity after T Cell–Depleted Allogeneic Transplantation Requires Symptomatic Virus Reactivation

Slides:

Advertisements

Similar presentations

Hematopoietic Stem Cell Transplantation in Australia and New Zealand,

Advertisements

Volume 17, Issue 9, Pages (September 2015)

WT1-specific T-cell responses in high-risk multiple myeloma patients undergoing allogeneic T cell–depleted hematopoietic stem cell transplantation and.

Engineering Human Peripheral Blood Stem Cell Grafts that Are Depleted of Naïve T Cells and Retain Functional Pathogen-Specific Memory T Cells Marie Bleakley,

Cytomegalovirus Viral Load and Virus-Specific Immune Reconstitution after Peripheral Blood Stem Cell versus Bone Marrow Transplantation Abraham Guerrero,

Rabbit Anti T-Lymphocyte Globulin Induces Apoptosis in Peripheral Blood Mononuclear Cell Compartments and Leukemia Cells, While Hematopoetic Stem Cells.

Depletion of Alloreactive Donor T Lymphocytes by CD95-Mediated Activation-Induced Cell Death Retains Antileukemic, Antiviral, and Immunoregulatory T Cell.

Functionally Active HIV-Specific T Cells that Target Gag and Nef Can Be Expanded from Virus-Naïve Donors and Target a Range of Viral Epitopes: Implications.

Safety of Live Attenuated High-Titer Varicella-Zoster Virus Vaccine in Pediatric Allogeneic Hematopoietic Stem Cell Transplantation Recipients Takahiro.

CD154 Expression Is Associated with Neutralizing Antibody Titer Levels Postinfluenza Vaccination in Stem Cell Transplant Patients and Healthy Adults

CMV-, EBV- and ADV-Specific T Cell Immunity: Screening and Monitoring of Potential Third-Party Donors to Improve Post-Transplantation Outcome Cinja Sukdolak,

Potential Role of a Mismatched HLA-Specific CTL Clone Developed Pre-Transplant in Graft Rejection following Cord Blood Transplantation Hiroto Narimatsu,

Induction of Immunity to Neuroblastoma Early after Syngeneic Hematopoietic Stem Cell Transplantation Using a Novel Mouse Tumor Vaccine Weiqing Jing,

Impaired Responses of Peripheral Blood Mononuclear Cells to Staphylococcal Superantigen in Patients with Severe Atopic Dermatitis: A Role of T Cell Apoptosis

Eosinophils from Hematopoietic Stem Cell Recipients Suppress Allogeneic T Cell Proliferation Jennie Andersson, Julia Cromvik, Madeleine Ingelsten, Christine.

Ping Zhang, Jieying Wu, Divino Deoliveira, Nelson J. Chao, Benny J

Increased Levels of Tumor Necrosis Factor α Are Associated with an Increased Risk of Cytomegalovirus Infection after Allogeneic Hematopoietic Stem Cell.

CD20-Targeted T Cells after Stem Cell Transplantation for High Risk and Refractory Non-Hodgkin's Lymphoma Lawrence G. Lum, Archana Thakur, Qin Liu, Abhinav.

CD8+ cytotoxic T lymphocytes isolated from allogeneic healthy donors recognize HLA class Ia/Ib–associated renal carcinoma antigens with ubiquitous or restricted.

Patient HLA-DP–Specific CD4+ T Cells from HLA-DPB1–Mismatched Donor Lymphocyte Infusion Can Induce Graft-versus-Leukemia Reactivity in the Presence or.

Protective antibody responses to pneumococcal conjugate vaccine after autologous hematopoietic stem cell transplantation Joseph H. Antin, Eva C. Guinan,

Altered Homeostasis of CD4+ Memory T Cells in Allogeneic Hematopoietic Stem Cell Transplant Recipients: Chronic Graft-versus-Host Disease Enhances T Cell.

Humoral Immune Reconstitution Kinetics after Allogeneic Hematopoietic Stem Cell Transplantation in Children: A Maturation Block of IgM Memory B Cells.

Mature dendritic cells pulsed with freeze–thaw cell lysates define an effective in vitro vaccine designed to elicit EBV-specific CD4+ and CD8+ T lymphocyte.

Mycophenolic Acid Inhibits Natural Killer Cell Proliferation and Cytotoxic Function: A Possible Disadvantage of Including Mycophenolate Mofetil in the.

Immunotherapy with Donor T Cells Sensitized with Overlapping Pentadecapeptides for Treatment of Persistent Cytomegalovirus Infection or Viremia Guenther.

Human CD4+CD25+ Cells in Combination with CD34+ Cells and Thymoglobulin to Prevent Anti-hematopoietic Stem Cell T Cell Alloreactivity Dolores Mahmud,

Growth and Differentiation Advantages of CD4+OX40+ T Cells from Allogeneic Hematopoietic Stem Cell Transplantation Recipients Takero Shindo, Takayuki.

CD11c+ dendritic cells and plasmacytoid DCs are activated by human cytomegalovirus and retain efficient T cell-stimulatory capability upon infection by.

Elevated Numbers of Immature/Transitional CD21− B Lymphocytes and Deficiency of Memory CD27+ B Cells Identify Patients with Active Chronic Graft-versus-Host.

FLT3 ligand administration after hematopoietic cell transplantation increases circulating dendritic cell precursors that can be activated by CpG oligodeoxynucleotides.

CD134-Allodepletion Allows Selective Elimination of Alloreactive Human T Cells without Loss of Virus-Specific and Leukemia-Specific Effectors Xupeng.

Identification of a Coordinated CD8 and CD4 T Cell Response Directed Against Mismatched HLA Class I Causing Severe Acute Graft-versus-Host Disease Avital.

Volume 17, Issue 9, Pages (September 2009)

Volume 138, Issue 3, Pages (March 2010)

Reconstitution of Natural Killer Cells in HLA-Matched HSCT after Reduced-Intensity Conditioning: Impact on Clinical Outcome Caroline Pical-Izard, Roberto.

Application of the ELISPOT assay to the characterization of CD8+ responses to Epstein-Barr virus antigens by Jie Yang, Victor M. Lemas, Ian W. Flinn, Chris.

Induction of chronic lymphocytic leukemia (CLL)–specific CD4- and CD8-mediated T-cell responses using RNA-transfected dendritic cells by Martin R. Müller,

Cytomegalovirus Immune Reconstitution Occurs in Recipients of Allogeneic Hematopoietic Cell Transplants Irrespective of Detectable Cytomegalovirus Infection

Suppression of natural killer cells in the presence of CD34+ blood progenitor cells and peripheral blood lymphocytes J. Clausen, M. Enk, B. Vergeiner,

Activated Allogeneic NK Cells as Suppressors of Alloreactive Responses

Human CD8+ memory and EBV-specific T cells show low alloreactivity in vitro and in CD34+ stem cell–engrafted NOD/SCID/IL-2Rγcnull mice Simone Thomas,

Bacteremia in Blood or Marrow Transplantation Patients: Clinical Risk Factors for Infection and Emerging Antibiotic Resistance Allison M. Bock, Qing.

Lymphocyte Subset Recovery and Outcome after Autologous Hematopoietic Stem Cell Transplantation for Plasma Cell Myeloma Jessica Rueff, Michael Medinger,

Effect of Ex Vivo Culture of CD34+ Bone Marrow Cells on Immune Reconstitution of XSCID Dogs Following Allogeneic Bone Marrow Transplantation Douglas.

Single Infusion of Donor Mononuclear Early Apoptotic Cells as Prophylaxis for Graft- versus-Host Disease in Myeloablative HLA-Matched Allogeneic Bone Marrow.

Molecular Monitoring of Minimal Residual Disease in the Peripheral Blood of Patients with Multiple Myeloma Mark Korthals, Nina Sehnke, Ralf Kronenwett,

Amotosalen-treated donor T cells have polyclonal antigen-specific long-term function without graft-versus-host disease after allogeneic bone marrow transplantation

B Cells and Transplantation: An Educational Resource

A comparison of gene transfer and antigen-loaded dendritic cells for the generation of CD4+ and CD8+ cytomegalovirus-specific T cells in HLA-A2+ and HLA-A2−

Quantification of Acute Lymphoblastic Leukemia Clonotypes in Leukapheresed Peripheral Blood Progenitor Cells Predicts Relapse Risk after Autologous Hematopoietic.

David J. Chung, MD, PhD, Katherine B. Pronschinske, Justin A

Protective Immunity Transferred by Infusion of Cytomegalovirus-Specific CD8+ T Cells within Donor Grafts: Its Associations with Cytomegalovirus Reactivation.

Disparity in Survival Outcome after Hematopoietic Stem Cell Transplantation for Hematologic Malignancies According to Area of Primary Residence Keshav.

Volume 13, Issue 2, Pages (February 2006)

Varicella-Zoster Reactivation after Allogeneic Stem Cell Transplantation without Routine Prophylaxis—The Incidence Remains High Ola Blennow, Gustav Fjaertoft,

Human CD4+ T Lymphocytes with Remarkable Regulatory Functions on Dendritic Cells and Nickel-Specific Th1 Immune Responses Andrea Cavani, Francesca Nasorri,

Possible Impact of Cytomegalovirus-Specific CD8+ T Cells on Immune Reconstitution and Conversion to Complete Donor Chimerism after Allogeneic Stem Cell.

Cord Blood Nucleated Cells Induce Delayed T Cell Alloreactivity

Allogeneic Hematopoietic Stem Cell Transplantation in FLT3-ITD–Positive Acute Myelogenous Leukemia: The Role for FLT3 Tyrosine Kinase Inhibitors Post-

Potential Role of a Mismatched HLA-Specific CTL Clone Developed Pre-Transplant in Graft Rejection following Cord Blood Transplantation Hiroto Narimatsu,

Unrelated Donor Hematopoietic Cell Transplantation: Factors Associated with a Better HLA Match Jason Dehn, Mukta Arora, Stephen Spellman, Michelle Setterholm,

Varicella-Zoster Virus Disease Is More Frequent after Cord Blood Than after Bone Marrow Transplantation Kristel Vandenbosch, Philippe Ovetchkine, Martin.

Mammen Chandy Biology of Blood and Marrow Transplantation

Quantitative Assessment of T Cell Clonotypes in Human Acute Graft-versus-Host Disease Tissues Daisuke Koyama, Makoto Murata, Ryo Hanajiri, Tomohiro Akashi,

Detection of Antigen-Specific B Cells in Patients with Pemphigus Vulgaris by Enzyme- Linked Immunospot Assay: Requirement of T Cell Collaboration for Autoantibody.

Human Herpes Virus 6 Plasma DNA Positivity after Hematopoietic Stem Cell Transplantation in Children: an Important Risk Factor for Clinical Outcome P.J.

Hematopoietic Stem Cell Transplantation in Australia and New Zealand,

What Role Is There for Antithymocyte Globulin in Allogeneic Nonmyeloablative Canine Hematopoietic Cell Transplantation? Razvan Diaconescu, Marie-Térèse.

Graft Monocytic Myeloid-Derived Suppressor Cell Content Predicts the Risk of Acute Graft-versus-Host Disease after Allogeneic Transplantation of Granulocyte.

Presentation transcript:

Recovery of Varicella-Zoster Virus–Specific T Cell Immunity after T Cell–Depleted Allogeneic Transplantation Requires Symptomatic Virus Reactivation Eva Distler, Elke Schnürer, Eva Wagner, Charis von Auer, Bodo Plachter, Daniela Wehler, Christoph Huber, Karin Kolbe, Ralf Georg Meyer, Wolfgang Herr Biology of Blood and Marrow Transplantation Volume 14, Issue 12, Pages 1417-1424 (December 2008) DOI: 10.1016/j.bbmt.2008.09.004 Copyright © 2008 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 1 VZV lysate is recognized by CD4+ memory T cells. A, PBMCs derived from VZV-seropositive healthy donor 1 were analyzed for reactivity to VZV-infected and uninfected Vero cell lysates in an IFN-γ ELISPOT assay. Lysates were added at titrated concentrations to the assay medium. Data are means of duplicate wells and are representative of 6 experiments in 3 different healthy virus carriers. B, CD4+ and CD8+ T cells were selected from PBMCs of VZV-seropositive healthy donor 2 and incubated with lysate-loaded autologous dendritic cells in ELISPOT plates. Dendritic cells were induced to mature after the addition of lysate preparations, which is a suitable strategy for promoting lysate-reactive CD8+ T cell responses [15]. C, ELISPOT reactivity to VZV lysate in PBMCs of seropositive healthy donor 3 was inhibited by monoclonal antibodies with blocking activity against HLA-DR, but not against HLA-class I. Data in panels B and C are means of triplicate wells and are representative of experiments in 5 different healthy immune donors. Biology of Blood and Marrow Transplantation 2008 14, 1417-1424DOI: (10.1016/j.bbmt.2008.09.004) Copyright © 2008 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 2 Quantification of VZV-reactive T cells in healthy immune and nonimmune donors. Diagrams show results of IFN-γ ELISPOT reactivity to VZV lysate in PBMCs of 15 seropositive and 5 seronegative healthy donors. The frequency of VZV-reactive T cells/mL of peripheral blood was calculated from the SFC count per 5 × 105 plated PBMCs and the PBMC count/mL of peripheral blood. ELISPOT reactivity to PHA did not differ significantly among individual PBMC samples (data not shown). PB, peripheral blood. Biology of Blood and Marrow Transplantation 2008 14, 1417-1424DOI: (10.1016/j.bbmt.2008.09.004) Copyright © 2008 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 3 Reconstitution of VZV-specific T cell immunity on posttransplantation herpes zoster. Patients 1 to 5 developed zoster during the first year after undergoing T cell–depleted allo-HSCT. Diagrams show the frequencies of VZV-reactive T cells in leukapheresis-derived PBMCs of stem cell donors before transplantation and in PBMCs of corresponding patients at various time points after transplantation. Results were obtained by IFN-γ ELISPOT assay using VZV lysate as the antigen source. Reactivity to uninfected control lysate was not found in any sample. Diagrams also include data of VZV-specific IgM (+, positive; -, negative) and VZV-specific IgG (mU/mL). Arrows indicate time points of zoster onset. SD, stem cell donor; DU, HLA-disparate unrelated; MU, HLA-matched unrelated; MS, HLA-matched sibling; Pat, patient; PB, peripheral blood. Biology of Blood and Marrow Transplantation 2008 14, 1417-1424DOI: (10.1016/j.bbmt.2008.09.004) Copyright © 2008 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 4 HLA restriction of VZV-reactive T cells during the first weeks after zoster. Shown is IFN-γ ELISPOT reactivity to VZV lysate in PBMCs of patients 1 and 5 isolated on days 14 and 35 after zoster onset, respectively. The assay medium contained mAbs for blocking HLA-class I or HLA-DR. Biology of Blood and Marrow Transplantation 2008 14, 1417-1424DOI: (10.1016/j.bbmt.2008.09.004) Copyright © 2008 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 5 Failure to reconstitute VZV-specific T cells in patients without zoster. Patients 6 to 17 did not develop zoster during the first year after T cell–depleted allo-HSCT. Diagrams show the frequency of VZV-reactive T cells in leukapheresis-derived PBMCs of stem cell donors before transplantation and in PBMCs of corresponding patients at different time points after transplantation. PBMCs of stem cell donors 12, 14, 16, and 17 were not available. Results were obtained by IFN-γ ELISPOT assay. For abbreviations, see Figure 3. Biology of Blood and Marrow Transplantation 2008 14, 1417-1424DOI: (10.1016/j.bbmt.2008.09.004) Copyright © 2008 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 6 Detection of VZV reactivity by proliferation assay. PBMCs isolated from patients prior to and after disease manifestation, as well as PBMCs from healthy immune and nonimmune donors (HD), were incubated for 6 days with 1 μg/mL of VZV-infected Vero cell lysate or uninfected control lysate, respectively. Medium and PHA (not shown) served as controls. T cell proliferation was measured by 3H-thymidine uptake for the last 18 hours of incubation on day 6. Prezoster PBMCs were derived at 2.75 months (patient 1), 0.75 month (patient 3), 4.5 months (patient 4), and 2.25 months (patient 5) after HSCT. Postzoster PBMCs were obtained at 4.75 months (patient 1), 3 months (patient 3), 6.25 months (patient 4), and 10.75 months (patient 5) after HSCT. For correlation with ELISPOT data, see Figure 3. Biology of Blood and Marrow Transplantation 2008 14, 1417-1424DOI: (10.1016/j.bbmt.2008.09.004) Copyright © 2008 American Society for Blood and Marrow Transplantation Terms and Conditions