Absence of major histocompatibility complex class I on neural stem cells does not permit natural killer cell killing and prevents recognition by alloreactive cytotoxic T lymphocytes in vitro

Michele Mammolenti, Shyam Cajavelli, Pantelis Tsoulfas, Robert B Levy

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Abstract

Potential applications of neural stem cells (NSCs) for transplantation requires understanding myosin heavy chain (MHC) expression and the ability of T cells and natural killer (NK) cells to recognize this progenitor population. Cells from the cortices of day-13 embryonic (E13) B6 (H-2b) mice were explanted and cultured to expand NSCs. Analysis of P2-P17-cultured cells using anti-MHC class I/II monoclonal antibodies (mAbs) showed marginal expression of both products. Although recombinant murine interferon-gamma (rmIFNγ) exposure did not alter the multipotential capacity of these stem cells, titration of mrIFNγ NSC cultures demonstrated that MHC molecules could be strongly upregulated after addition of 3 ng/ml rmIFNγ for 60 hours. To assess the susceptibility of NSCs with low or absent versus high levels of MHC expression to lysis by cytotoxic T lymphocyte (CTL) and NK populations, untreated and rmIFNγ-treated NSC target cells were examined. Untreated NSCs were not recognized by BALB/c (H-2d) allospecific anti-H-2 b CTL, consistent with the mAb findings; however, upregulation of MHC products on both early and later passaged NSCs resulted in their efficient lysis by CTL. NK cells were prepared from syngeneic B6 or allogeneic BALB/c mice. Although NK cells effectively killed control YAC-1 target cells, these effectors did not kill MHC-deficient (or expressing) NSC targets. Thus, similar to hematopoietic, embryonic, and mesenchymal stem cell populations, unmanipulated NSCs are not readily killed by T and NK cells. These findings suggest that following transplant into syngeneic or allogeneic recipients, NSCs may exhibit diminished susceptibility to clearance by host T- and NK-cell populations.

Original languageEnglish
Pages (from-to)1101-1110
Number of pages10
JournalStem Cells
Volume22
Issue number6
StatePublished - Nov 26 2004

Fingerprint

Neural Stem Cells
Cytotoxic T-Lymphocytes
Major Histocompatibility Complex
Natural Killer Cells
Myosin Heavy Chains
Interferon-gamma
Natural Killer T-Cells
Population
In Vitro Techniques
Stem Cell Transplantation
Embryonic Stem Cells
Hematopoietic Stem Cells
Mesenchymal Stromal Cells
Cultured Cells
Up-Regulation
Stem Cells
Cell Culture Techniques
Monoclonal Antibodies
T-Lymphocytes
Transplants

Keywords

  • Cytotoxicity
  • Natural killer recognition Myosin heavy chain expression
  • Neural stem cells
  • T-cell recognition

ASJC Scopus subject areas

  • Cell Biology

Cite this

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title = "Absence of major histocompatibility complex class I on neural stem cells does not permit natural killer cell killing and prevents recognition by alloreactive cytotoxic T lymphocytes in vitro",
abstract = "Potential applications of neural stem cells (NSCs) for transplantation requires understanding myosin heavy chain (MHC) expression and the ability of T cells and natural killer (NK) cells to recognize this progenitor population. Cells from the cortices of day-13 embryonic (E13) B6 (H-2b) mice were explanted and cultured to expand NSCs. Analysis of P2-P17-cultured cells using anti-MHC class I/II monoclonal antibodies (mAbs) showed marginal expression of both products. Although recombinant murine interferon-gamma (rmIFNγ) exposure did not alter the multipotential capacity of these stem cells, titration of mrIFNγ NSC cultures demonstrated that MHC molecules could be strongly upregulated after addition of 3 ng/ml rmIFNγ for 60 hours. To assess the susceptibility of NSCs with low or absent versus high levels of MHC expression to lysis by cytotoxic T lymphocyte (CTL) and NK populations, untreated and rmIFNγ-treated NSC target cells were examined. Untreated NSCs were not recognized by BALB/c (H-2d) allospecific anti-H-2 b CTL, consistent with the mAb findings; however, upregulation of MHC products on both early and later passaged NSCs resulted in their efficient lysis by CTL. NK cells were prepared from syngeneic B6 or allogeneic BALB/c mice. Although NK cells effectively killed control YAC-1 target cells, these effectors did not kill MHC-deficient (or expressing) NSC targets. Thus, similar to hematopoietic, embryonic, and mesenchymal stem cell populations, unmanipulated NSCs are not readily killed by T and NK cells. These findings suggest that following transplant into syngeneic or allogeneic recipients, NSCs may exhibit diminished susceptibility to clearance by host T- and NK-cell populations.",
keywords = "Cytotoxicity, Natural killer recognition Myosin heavy chain expression, Neural stem cells, T-cell recognition",
author = "Michele Mammolenti and Shyam Cajavelli and Pantelis Tsoulfas and Levy, {Robert B}",
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T1 - Absence of major histocompatibility complex class I on neural stem cells does not permit natural killer cell killing and prevents recognition by alloreactive cytotoxic T lymphocytes in vitro

AU - Mammolenti, Michele

AU - Cajavelli, Shyam

AU - Tsoulfas, Pantelis

AU - Levy, Robert B

PY - 2004/11/26

Y1 - 2004/11/26

N2 - Potential applications of neural stem cells (NSCs) for transplantation requires understanding myosin heavy chain (MHC) expression and the ability of T cells and natural killer (NK) cells to recognize this progenitor population. Cells from the cortices of day-13 embryonic (E13) B6 (H-2b) mice were explanted and cultured to expand NSCs. Analysis of P2-P17-cultured cells using anti-MHC class I/II monoclonal antibodies (mAbs) showed marginal expression of both products. Although recombinant murine interferon-gamma (rmIFNγ) exposure did not alter the multipotential capacity of these stem cells, titration of mrIFNγ NSC cultures demonstrated that MHC molecules could be strongly upregulated after addition of 3 ng/ml rmIFNγ for 60 hours. To assess the susceptibility of NSCs with low or absent versus high levels of MHC expression to lysis by cytotoxic T lymphocyte (CTL) and NK populations, untreated and rmIFNγ-treated NSC target cells were examined. Untreated NSCs were not recognized by BALB/c (H-2d) allospecific anti-H-2 b CTL, consistent with the mAb findings; however, upregulation of MHC products on both early and later passaged NSCs resulted in their efficient lysis by CTL. NK cells were prepared from syngeneic B6 or allogeneic BALB/c mice. Although NK cells effectively killed control YAC-1 target cells, these effectors did not kill MHC-deficient (or expressing) NSC targets. Thus, similar to hematopoietic, embryonic, and mesenchymal stem cell populations, unmanipulated NSCs are not readily killed by T and NK cells. These findings suggest that following transplant into syngeneic or allogeneic recipients, NSCs may exhibit diminished susceptibility to clearance by host T- and NK-cell populations.

AB - Potential applications of neural stem cells (NSCs) for transplantation requires understanding myosin heavy chain (MHC) expression and the ability of T cells and natural killer (NK) cells to recognize this progenitor population. Cells from the cortices of day-13 embryonic (E13) B6 (H-2b) mice were explanted and cultured to expand NSCs. Analysis of P2-P17-cultured cells using anti-MHC class I/II monoclonal antibodies (mAbs) showed marginal expression of both products. Although recombinant murine interferon-gamma (rmIFNγ) exposure did not alter the multipotential capacity of these stem cells, titration of mrIFNγ NSC cultures demonstrated that MHC molecules could be strongly upregulated after addition of 3 ng/ml rmIFNγ for 60 hours. To assess the susceptibility of NSCs with low or absent versus high levels of MHC expression to lysis by cytotoxic T lymphocyte (CTL) and NK populations, untreated and rmIFNγ-treated NSC target cells were examined. Untreated NSCs were not recognized by BALB/c (H-2d) allospecific anti-H-2 b CTL, consistent with the mAb findings; however, upregulation of MHC products on both early and later passaged NSCs resulted in their efficient lysis by CTL. NK cells were prepared from syngeneic B6 or allogeneic BALB/c mice. Although NK cells effectively killed control YAC-1 target cells, these effectors did not kill MHC-deficient (or expressing) NSC targets. Thus, similar to hematopoietic, embryonic, and mesenchymal stem cell populations, unmanipulated NSCs are not readily killed by T and NK cells. These findings suggest that following transplant into syngeneic or allogeneic recipients, NSCs may exhibit diminished susceptibility to clearance by host T- and NK-cell populations.

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KW - T-cell recognition

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