Preservation of antigen-specific functions of αβ T cells and B cells removed from hematopoietic stem cell transplants suggests their use as an alternative cell source for advanced manipulation and adoptive immunotherapy

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Abstract

Hematopoietic stem cell transplantation is standard therapy for numerous hematological diseases. The use of haploidentical donors, sharing half of the HLA alleles with the recipient, has facilitated the use of this procedure as patients can rely on availability of a haploidentical donor within their family. Since HLA disparity increases the risk of graft-versus-host disease, T-cell depletion has been used to remove alloreactive lymphocytes from the graft. Selective removal of αβ T cells, which encompass the alloreactive repertoire, combined with removal of B cells to prevent EBV-related lymphoproliferative disease, proved safe and effective in clinical studies. Depleted αβ T cells and B cells are generally discarded as by-products. Considering the possible use of donor T cells for donor lymphocyte infusions or for generation of pathogen-specific T cells as mediators of graft-versus-infection effect, we tested whether cells in the discarded fractions were functionally intact. Response to alloantigens and to viral antigens comparable to that of unmanipulated cells indicated a functional integrity of αβ T cells, in spite of the manipulation used for their depletion. Furthermore, B cells proved to be efficient antigen-presenting cells, indicating that antigen uptake, processing, and presentation were fully preserved. Therefore, we propose that separated αβ T lymphocytes could be employed for obtaining pathogen-specific T cells, applying available methods for positive selection, which eventually leads to indirect allodepletion. In addition, these functional T cells could undergo additional manipulation, such as direct allodepletion or genetic modification.

Original languageEnglish
Article number332
JournalFrontiers in Immunology
Volume8
Issue numberMAR
DOIs
Publication statusPublished - Mar 23 2017

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Adoptive Immunotherapy
Hematopoietic Stem Cells
B-Lymphocytes
T-Lymphocytes
Transplants
Antigens
Tissue Donors
Antigen Presentation
Lymphocytes
Isoantigens
Viral Antigens
Hematologic Diseases
Hematopoietic Stem Cell Transplantation
Graft vs Host Disease
Antigen-Presenting Cells
Human Herpesvirus 4
Alleles

Keywords

  • Alloreactivity
  • Antigen-induced activation
  • B-cell presentation
  • Graft manipulation
  • HLA-haploidentical transplantation
  • αβ T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

@article{241e8c01cbe740b988b6a0feeb478fa9,
title = "Preservation of antigen-specific functions of αβ T cells and B cells removed from hematopoietic stem cell transplants suggests their use as an alternative cell source for advanced manipulation and adoptive immunotherapy",
abstract = "Hematopoietic stem cell transplantation is standard therapy for numerous hematological diseases. The use of haploidentical donors, sharing half of the HLA alleles with the recipient, has facilitated the use of this procedure as patients can rely on availability of a haploidentical donor within their family. Since HLA disparity increases the risk of graft-versus-host disease, T-cell depletion has been used to remove alloreactive lymphocytes from the graft. Selective removal of αβ T cells, which encompass the alloreactive repertoire, combined with removal of B cells to prevent EBV-related lymphoproliferative disease, proved safe and effective in clinical studies. Depleted αβ T cells and B cells are generally discarded as by-products. Considering the possible use of donor T cells for donor lymphocyte infusions or for generation of pathogen-specific T cells as mediators of graft-versus-infection effect, we tested whether cells in the discarded fractions were functionally intact. Response to alloantigens and to viral antigens comparable to that of unmanipulated cells indicated a functional integrity of αβ T cells, in spite of the manipulation used for their depletion. Furthermore, B cells proved to be efficient antigen-presenting cells, indicating that antigen uptake, processing, and presentation were fully preserved. Therefore, we propose that separated αβ T lymphocytes could be employed for obtaining pathogen-specific T cells, applying available methods for positive selection, which eventually leads to indirect allodepletion. In addition, these functional T cells could undergo additional manipulation, such as direct allodepletion or genetic modification.",
keywords = "Alloreactivity, Antigen-induced activation, B-cell presentation, Graft manipulation, HLA-haploidentical transplantation, αβ T cells",
author = "Pira, {Giuseppina Li} and Cecca, {Stefano Di} and Simone Biagini and Elia Girolami and Elisabetta Cicchetti and Valentina Bertaina and Concetta Quintarelli and Ignazio Caruana and Barbarella Lucarelli and Pietro Merli and Daria Pagliara and Brescia, {Letizia Pomponia} and Alice Bertaina and Mauro Montanari and Franco Locatelli",
year = "2017",
month = "3",
day = "23",
doi = "10.3389/fimmu.2017.00332",
language = "English",
volume = "8",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Media S.A.",
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TY - JOUR

T1 - Preservation of antigen-specific functions of αβ T cells and B cells removed from hematopoietic stem cell transplants suggests their use as an alternative cell source for advanced manipulation and adoptive immunotherapy

AU - Pira, Giuseppina Li

AU - Cecca, Stefano Di

AU - Biagini, Simone

AU - Girolami, Elia

AU - Cicchetti, Elisabetta

AU - Bertaina, Valentina

AU - Quintarelli, Concetta

AU - Caruana, Ignazio

AU - Lucarelli, Barbarella

AU - Merli, Pietro

AU - Pagliara, Daria

AU - Brescia, Letizia Pomponia

AU - Bertaina, Alice

AU - Montanari, Mauro

AU - Locatelli, Franco

PY - 2017/3/23

Y1 - 2017/3/23

N2 - Hematopoietic stem cell transplantation is standard therapy for numerous hematological diseases. The use of haploidentical donors, sharing half of the HLA alleles with the recipient, has facilitated the use of this procedure as patients can rely on availability of a haploidentical donor within their family. Since HLA disparity increases the risk of graft-versus-host disease, T-cell depletion has been used to remove alloreactive lymphocytes from the graft. Selective removal of αβ T cells, which encompass the alloreactive repertoire, combined with removal of B cells to prevent EBV-related lymphoproliferative disease, proved safe and effective in clinical studies. Depleted αβ T cells and B cells are generally discarded as by-products. Considering the possible use of donor T cells for donor lymphocyte infusions or for generation of pathogen-specific T cells as mediators of graft-versus-infection effect, we tested whether cells in the discarded fractions were functionally intact. Response to alloantigens and to viral antigens comparable to that of unmanipulated cells indicated a functional integrity of αβ T cells, in spite of the manipulation used for their depletion. Furthermore, B cells proved to be efficient antigen-presenting cells, indicating that antigen uptake, processing, and presentation were fully preserved. Therefore, we propose that separated αβ T lymphocytes could be employed for obtaining pathogen-specific T cells, applying available methods for positive selection, which eventually leads to indirect allodepletion. In addition, these functional T cells could undergo additional manipulation, such as direct allodepletion or genetic modification.

AB - Hematopoietic stem cell transplantation is standard therapy for numerous hematological diseases. The use of haploidentical donors, sharing half of the HLA alleles with the recipient, has facilitated the use of this procedure as patients can rely on availability of a haploidentical donor within their family. Since HLA disparity increases the risk of graft-versus-host disease, T-cell depletion has been used to remove alloreactive lymphocytes from the graft. Selective removal of αβ T cells, which encompass the alloreactive repertoire, combined with removal of B cells to prevent EBV-related lymphoproliferative disease, proved safe and effective in clinical studies. Depleted αβ T cells and B cells are generally discarded as by-products. Considering the possible use of donor T cells for donor lymphocyte infusions or for generation of pathogen-specific T cells as mediators of graft-versus-infection effect, we tested whether cells in the discarded fractions were functionally intact. Response to alloantigens and to viral antigens comparable to that of unmanipulated cells indicated a functional integrity of αβ T cells, in spite of the manipulation used for their depletion. Furthermore, B cells proved to be efficient antigen-presenting cells, indicating that antigen uptake, processing, and presentation were fully preserved. Therefore, we propose that separated αβ T lymphocytes could be employed for obtaining pathogen-specific T cells, applying available methods for positive selection, which eventually leads to indirect allodepletion. In addition, these functional T cells could undergo additional manipulation, such as direct allodepletion or genetic modification.

KW - Alloreactivity

KW - Antigen-induced activation

KW - B-cell presentation

KW - Graft manipulation

KW - HLA-haploidentical transplantation

KW - αβ T cells

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U2 - 10.3389/fimmu.2017.00332

DO - 10.3389/fimmu.2017.00332

M3 - Article

VL - 8

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

IS - MAR

M1 - 332

ER -