Immune reconstitution and production of intracellular cytokines in t lymphocyte populations following autologous peripheral blood stem cell transplantation

Immune reconstitution and production of intracellular cytokines in t lymphocyte populations following autologous peripheral blood stem cell transplantation

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ABSTRACT For the better understanding of engraftment properties after autologous peripheral blood stem cell transplantation (PBSCT), hematopoietic recovery, immune reconstitution and


functional capacity of cytokine production in different lymphocyte populations were examined. In a prospective study, we examined 24 patients suffering from different malignancies after


autologous PBSCT. The examination intervals were 1, 3, 6 and 12 months after PBSCT. T cells, B cells and NK cells were analyzed using flow cytometry. The expression and kinetics of cytokines


in T lymphocytes were evaluated in 10 patients by intracellular staining of cytokines after PMA/ionomycin stimulation. We observed rapid hematopoietic engraftment proceeding to stable


long-term reconstitution. For CD3+ lymphocytes, a consistent reconstitution associated with an increase in CD3+CD8+ cytotoxic T cells was observed, whereas the CD3+CD4+ helper/inducer T


cells remained low (<200/μl). Impaired B lymphopoiesis with severe depression (<1%) was detected 1 month after PBSCT but recovered thereafter (12.8% after 3 months). The percentages of


cytokine-producing T cells and the mean fluorescence intensity (MFI) shifts suggested an insufficient capacity for producing IFNγ, in particular for CD3+CD4+ T cells, compared to healthy


volunteers early after PBSCT. Rapid hematopoietic recovery and partly impaired immune reconstitution, especially regarding the regeneration of B lymphocytes and T helper cells, was observed.


The CD4+ subpopulation remained low throughout the period of examination, whereas the B cells showed a delayed recovery after 3 months. Cytokine production proved to be sufficient after _in


vitro_ stimulation in T cell populations with the exception of IFNγ synthesis. _Bone Marrow Transplantation_ (2001) 28, 251–257. Access through your institution Buy or subscribe This is a


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MEMORY T-CELL INFUSIONS AFTER ΑΒ T CELL-DEPLETED HEMATOPOIETIC STEM CELL TRANSPLANTATION Article 17 November 2020 REFERENCES * Thomas ED . Marrow transplantation for malignant diseases _J


Clin Oncol_ 1983 1: 517–531 Article  CAS  PubMed  Google Scholar  * Juttner CA, To LB, Haylock DN _et al_. Circulating autologous stem cells collected in a very early remission from acute


non-lymphoblastic leukemia produce prompt but incomplete hematopoietic reconstitution after high-dose melphalan or supralethal chemoradiotherapy _Br J Haematol_ 1998 61: 739–745 Article 


Google Scholar  * Kessinger A, Armitage JO, Landwark JD _et al_. Autologous peripheral hematopoietic stem cell transplantation restores hematopoietic function following marrow ablative


therapy _Blood_ 1988 71: 723–727 CAS  PubMed  Google Scholar  * Armitage JO . Bone marrow transplantation _New Engl J Med_ 1994 330: 827–838 Article  CAS  PubMed  Google Scholar  * Gratwohl


A, Passweg J, Baldomero H, Hermans J . Blood and marrow transplantation activity in Europe 1997. European Group for Blood and Marrow Transplantation (EBMT) _Bone Marrow Transplant_ 1999 24:


231–245 Article  CAS  PubMed  Google Scholar  * Metcalf D . Hematopoietic Regulators: redundancy or subtlety? _Blood_ 1993 82: 3515–3523 CAS  PubMed  Google Scholar  * Lansdorp P .


Developmental changes in the function of hematopoietic stem cells _Exp Hematol_ 1995 23: 187–191 CAS  PubMed  Google Scholar  * To LB, Haylock DN, Simmons PJ _et al_. The biology and


clinical uses of blood stem cells _Blood_ 1997 89: 2233–2258 CAS  PubMed  Google Scholar  * Hoffman R, Rozler E, Chute J _et al_. Ex vivo expansion of human hematopoietic stem cells:


Implications for the modern blood bank _Vox Sang_ 1998 74: 259–264 Article  PubMed  Google Scholar  * Chao NJ, Schriber JR, Grimes K _et al_. Granulocyte colony-stimulating factor


‘mobilized’ peripheral blood progenitor cells accelerate granulocyte and platelet recovery after high dose chemotherapy _Blood_ 1993 81: 2031–2035 CAS  PubMed  Google Scholar  * Bensinger


WI, Weaver CH, Appelbaum FR _et al_. Transplantation of allogeneic peripheral blood stem cells mobilized by recombinant human granulocyte colony-stimulating factor _Blood_ 1995 85: 1655–1658


CAS  PubMed  Google Scholar  * Olivieri A, Offidani M, Montanari M _et al_. Factors affecting hemopoietic recovery after high-dose therapy and autologous peripheral blood progenitor cell


transplantation: a single center experience _Haematologica_ 1998 83: 329–337 CAS  PubMed  Google Scholar  * Beguin Y, Baudoux E, Sautois B _et al_. Hematopoietic recovery in cancer patients


after transplantation of autologous peripheral blood CD34+ cells or unmanipulated peripheral blood stem and progenitor cells _Transfusion_ 1998 38: 199–208 Article  CAS  PubMed  Google


Scholar  * Beelen DW, Ottinger HD, Elmaagacli A _et al_. Transplantation of Filgrastim mobilized peripheral blood stem cell from HLA-identical sibling or alternative family donors in


patients with hematological malignancies: a prospective comparison on clinical outcome, immune reconstitution, and hematopoietic chimerism _Blood_ 1997 90: 4725–4735 CAS  PubMed  Google


Scholar  * Henon PR, Liang H, Beckwirth G _et al_. Comparison of hematopoietic and immune recovery after autologous bone marrow transplantation or blood stem cell transplants _Bone Marrow


Transplant_ 1992 9: 285–291 CAS  PubMed  Google Scholar  * Ottinger HD, Beelen DW, Scheulen B _et al_. Improved immune reconstitution after allotransplantation of peripheral blood stem cells


instead of bone marrow _Blood_ 1996 88: 2775–2779 CAS  PubMed  Google Scholar  * Parkman R, Weinberg KI . Immunological reconstitution following bone marrow transplantation _Immunol Rev_


1997 157: 73–78 Article  CAS  PubMed  Google Scholar  * Martinez C, Urbano-Ispizua A, Rozman C _et al_. Immune reconstitution following allogenic peripheral blood progenitor cell


transplantation: Comparison of recipients of positive CD34+ selected grafts with recipients of unmanipulated grafts _Exp Hematol_ 1999 27: 561–568 Article  CAS  PubMed  Google Scholar  *


Jung T, Schauer U, Heusser C _et al_. Detection of intracellular cytokines by flow-cytometry _J Immunol Meth_ 1993 159: 197–202 Article  CAS  Google Scholar  * Mascher B, Schlenke P,


Seyfarth M . Expression and kinetics of cytokines determined by intracellular staining using flow cytometry _J Immunol Meth_ 1999 223: 115–121 Article  CAS  Google Scholar  * Pecora AL .


Impact of stem cell dose on hematopoietic recovery in autologous blood stem cell recipients _Bone Marrow Transplant_ 1999 23: (Suppl. 2) 7–12 Article  Google Scholar  * Charbonnier A, Sainty


D, Faucher C _et al_. Immune reconstitution after blood cell transplantation _Hematol Cell Ther_ 1997 39: 261–264 Article  CAS  PubMed  Google Scholar  * Bomberger C, Singh-Jairam M, Rodey


G _et al_. Lymphoid reconstitution after autologous PBSC transplantation with FACS-sorted CD34+ hematopoietic progenitors _Blood_ 1998 91: 2588–2600 CAS  PubMed  Google Scholar  * Divine M,


Boutolleau D, Delfau-Larue MH _et al_. Poor lymphocyte recovery following CD34 selected autologous peripheral stem cell transplantation for non-Hodgkin's lymphoma _Br J Haematol_ 1999


105: 349–360 Article  CAS  PubMed  Google Scholar  * Kook H, Goldman F, Padley D _et al_. Reconstitution after unrelated or partially matched T-cell-depleted bone-marrow transplantation in


children: immunophenotypic analysis and factors affecting the speed of recovery _Blood_ 1996 88: 1089–1097 CAS  PubMed  Google Scholar  * del Canizo MC, Lopez N, Vasquez L _et al_.


Hematopoietic damage prior to PBSCT and its influence on hematopoietic recovery _Haematologica_ 1999 84: 511–516 CAS  PubMed  Google Scholar  * Weaver CH, Longin K, Buckner CD _et al_.


Lymphocyte content in peripheral blood mononuclear cells collected after administration of recombinant human granulocyte colony-stimulating factor _Bone Marrow Transplant_ 1994 84: 411–415


Google Scholar  * Mackall CL, Fleisher TA, Brown MR _et al_. Age, thymopoiesis and CD4+ T-lymphocyte regeneration after intensive chemotherapy _New Engl J Med_ 1995 332: 143–147 Article  CAS


  PubMed  Google Scholar  * Mackall CL, Fleisher TA, Brown MR _et al_. Distinctions between CD8+ and CD4+ T-cell regenerative pathways result in prolonged T-cell subset imbalance after


intensive chemotherapy _Blood_ 1997 89: 3700–3707 CAS  PubMed  Google Scholar  * Sanders ME, Makgoba MW, Shaw S . Human naive and memory T-cells: reinterpretation of helper-inducer and


supressor-inducer subsets _Immunol Today_ 1988 9: 195–201 Article  CAS  PubMed  Google Scholar  * Heitger A, Neu N, Kern H _et al_. Essential role of the thymus to reconstitute naive


(CD45RA+) T-helper cells after human allogeneic bone marrow transplantation _Blood_ 1997 90: 850–857 CAS  PubMed  Google Scholar  * Koehne G, Zeller W, Stockschlaeger M _et al_. Phenotype of


subsets after autologous peripheral blood stem cell transplantation _Bone Marrow Transplant_ 1997 19: 149–156 Article  CAS  PubMed  Google Scholar  * Hakim FT, Cepeda R, Kaimei S _et al_.


Constraints on CD4 recovery postchemotherapy in adults: thymic insufficiency and apoptotic decline of expanded peripheral CD4 cells _Blood_ 1997 90: 3789–3798 CAS  PubMed  Google Scholar 


Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Institute for Immunology and Transfusion Medicine, University of Lübeck School of Medicine, Germany P Schlenke, S


Sheikhzadeh & H Kirchner * Department of Internal Medicine, Section Hematology and Oncology, University of Lübeck School of Medicine, Germany K Weber & T Wagner Authors * P Schlenke


View author publications You can also search for this author inPubMed Google Scholar * S Sheikhzadeh View author publications You can also search for this author inPubMed Google Scholar * K


Weber View author publications You can also search for this author inPubMed Google Scholar * T Wagner View author publications You can also search for this author inPubMed Google Scholar * H


Kirchner View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Schlenke,


P., Sheikhzadeh, S., Weber, K. _et al._ Immune reconstitution and production of intracellular cytokines in T lymphocyte populations following autologous peripheral blood stem cell


transplantation. _Bone Marrow Transplant_ 28, 251–257 (2001). https://doi.org/10.1038/sj.bmt.1703121 Download citation * Received: 21 December 2000 * Accepted: 15 May 2001 * Published: 04


September 2001 * Issue Date: 01 August 2001 * DOI: https://doi.org/10.1038/sj.bmt.1703121 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get


shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * high-dose


chemotherapy * autologous stem cell transplantation * CD34+ cells * immune reconstitution * lymphocyte subsets * intracellular cytokines