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 language | English |
|---|---|
| Pages (from-to) | 1101-1110 |
| Number of pages | 10 |
| Journal | Stem Cells |
| Volume | 22 |
| Issue number | 6 |
| State | Published - Nov 26 2004 |
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Keywords
- Cytotoxicity
- Natural killer recognition Myosin heavy chain expression
- Neural stem cells
- T-cell recognition
ASJC Scopus subject areas
- Cell Biology
Cite this
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. / Mammolenti, Michele; Cajavelli, Shyam; Tsoulfas, Pantelis; Levy, Robert B.
In: Stem Cells, Vol. 22, No. 6, 26.11.2004, p. 1101-1110.Research output: Contribution to journal › Article
}
TY - JOUR
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.
KW - Cytotoxicity
KW - Natural killer recognition Myosin heavy chain expression
KW - Neural stem cells
KW - T-cell recognition
UR - http://www.scopus.com/inward/record.url?scp=8644220665&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=8644220665&partnerID=8YFLogxK
M3 - Article
C2 - 15536199
AN - SCOPUS:8644220665
VL - 22
SP - 1101
EP - 1110
JO - Stem Cells
JF - Stem Cells
SN - 1066-5099
IS - 6
ER -