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MHC Class I Expression by Donor Hematopoietic Stem Cells Is Required to Prevent NK Cell Attack in Allogeneic, but Not Syngeneic Recipient Mice.

Hirata Y, Li HW, Takahashi K, Ishii H, Sykes M, Fujisaki J - PLoS ONE (2015)

Bottom Line: NK cells resist engraftment of syngeneic and allogeneic bone marrow (BM) cells lacking major histocompatibility (MHC) class I molecules, suggesting a critical role for donor MHC class I molecules in preventing NK cell attack against donor hematopoietic stem and progenitor cells (HSPCs), and their derivatives.In contrast, syngeneic MHC class I KO differentiated hematopoietic cells and allogeneic MHC class I KO HSPCs were rejected in a manner that was significantly inhibited by NK cell depletion.The data indicate that donor MHC class I molecules are required to prevent NK cell-mediated rejection of syngeneic differentiated cells and allogeneic HSPCs, but not of syngeneic HSPCs.

View Article: PubMed Central - PubMed

Affiliation: Columbia Center for Translational Immunology, Department of Medicine, Surgery and Microbiology/Immunology, College of Physicians and Surgeons, Columbia University, New York, New York, United States of America.

ABSTRACT
NK cells resist engraftment of syngeneic and allogeneic bone marrow (BM) cells lacking major histocompatibility (MHC) class I molecules, suggesting a critical role for donor MHC class I molecules in preventing NK cell attack against donor hematopoietic stem and progenitor cells (HSPCs), and their derivatives. However, using high-resolution in vivo imaging, we demonstrated here that syngeneic MHC class I knockout (KO) donor HSPCs persist with the same survival frequencies as wild-type donor HSPCs. In contrast, syngeneic MHC class I KO differentiated hematopoietic cells and allogeneic MHC class I KO HSPCs were rejected in a manner that was significantly inhibited by NK cell depletion. In vivo time-lapse imaging demonstrated that mice receiving allogeneic MHC class I KO HSPCs showed a significant increase in NK cell motility and proliferation as well as frequencies of NK cell contact with and killing of HSPCs as compared to mice receiving wild-type HSPCs. The data indicate that donor MHC class I molecules are required to prevent NK cell-mediated rejection of syngeneic differentiated cells and allogeneic HSPCs, but not of syngeneic HSPCs.

No MeSH data available.


Related in: MedlinePlus

The lack of MHC class I expression by donor cells leads to rejection of allogeneic HSPCs and syngeneic differentiated cells, but not of syngeneic HSPCs.(a, b) The numbers of B6 MHC class I KO and wild-type HSPCs in the identical regions (2540 μm (x) × 2570 μm (y) x 150 μm (z)) of the skull BMs of non-irradiated BALB/c mice on day 1 (a: 3 recipients/group in an independent experiment), and day 12 (b: 8 vs 6 recipients/group pooled from three independent experiments). (c) The numbers of B6 MHC class I KO and wild-type HSPCs in the skull BMs of non-irradiated B6 mice on day 12 (8 vs 6 recipients/group pooled from three independent experiments). (d) The numbers of B6 MHC class I KO and wild-type lineage+ differentiated cells in the identical regions (2540 μm (x) × 2570 μm (y) x 150 μm (z)) of the skull BMs of B6 mice on day 7 (3 recipients/group in an independent experiment).
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pone.0141785.g001: The lack of MHC class I expression by donor cells leads to rejection of allogeneic HSPCs and syngeneic differentiated cells, but not of syngeneic HSPCs.(a, b) The numbers of B6 MHC class I KO and wild-type HSPCs in the identical regions (2540 μm (x) × 2570 μm (y) x 150 μm (z)) of the skull BMs of non-irradiated BALB/c mice on day 1 (a: 3 recipients/group in an independent experiment), and day 12 (b: 8 vs 6 recipients/group pooled from three independent experiments). (c) The numbers of B6 MHC class I KO and wild-type HSPCs in the skull BMs of non-irradiated B6 mice on day 12 (8 vs 6 recipients/group pooled from three independent experiments). (d) The numbers of B6 MHC class I KO and wild-type lineage+ differentiated cells in the identical regions (2540 μm (x) × 2570 μm (y) x 150 μm (z)) of the skull BMs of B6 mice on day 7 (3 recipients/group in an independent experiment).

Mentions: On day 1, the numbers of DiD-labeled B6 wild-type HSPCs and B6 MHC class I KO HSPCs in identical regions of the skull BMs were comparable in BALB/c recipient mice (Fig 1A). This indicates that the lack of MHC class I of donor HSPCs did not affect HSPC homing or rejection in the circulation.


MHC Class I Expression by Donor Hematopoietic Stem Cells Is Required to Prevent NK Cell Attack in Allogeneic, but Not Syngeneic Recipient Mice.

Hirata Y, Li HW, Takahashi K, Ishii H, Sykes M, Fujisaki J - PLoS ONE (2015)

The lack of MHC class I expression by donor cells leads to rejection of allogeneic HSPCs and syngeneic differentiated cells, but not of syngeneic HSPCs.(a, b) The numbers of B6 MHC class I KO and wild-type HSPCs in the identical regions (2540 μm (x) × 2570 μm (y) x 150 μm (z)) of the skull BMs of non-irradiated BALB/c mice on day 1 (a: 3 recipients/group in an independent experiment), and day 12 (b: 8 vs 6 recipients/group pooled from three independent experiments). (c) The numbers of B6 MHC class I KO and wild-type HSPCs in the skull BMs of non-irradiated B6 mice on day 12 (8 vs 6 recipients/group pooled from three independent experiments). (d) The numbers of B6 MHC class I KO and wild-type lineage+ differentiated cells in the identical regions (2540 μm (x) × 2570 μm (y) x 150 μm (z)) of the skull BMs of B6 mice on day 7 (3 recipients/group in an independent experiment).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4636372&req=5

pone.0141785.g001: The lack of MHC class I expression by donor cells leads to rejection of allogeneic HSPCs and syngeneic differentiated cells, but not of syngeneic HSPCs.(a, b) The numbers of B6 MHC class I KO and wild-type HSPCs in the identical regions (2540 μm (x) × 2570 μm (y) x 150 μm (z)) of the skull BMs of non-irradiated BALB/c mice on day 1 (a: 3 recipients/group in an independent experiment), and day 12 (b: 8 vs 6 recipients/group pooled from three independent experiments). (c) The numbers of B6 MHC class I KO and wild-type HSPCs in the skull BMs of non-irradiated B6 mice on day 12 (8 vs 6 recipients/group pooled from three independent experiments). (d) The numbers of B6 MHC class I KO and wild-type lineage+ differentiated cells in the identical regions (2540 μm (x) × 2570 μm (y) x 150 μm (z)) of the skull BMs of B6 mice on day 7 (3 recipients/group in an independent experiment).
Mentions: On day 1, the numbers of DiD-labeled B6 wild-type HSPCs and B6 MHC class I KO HSPCs in identical regions of the skull BMs were comparable in BALB/c recipient mice (Fig 1A). This indicates that the lack of MHC class I of donor HSPCs did not affect HSPC homing or rejection in the circulation.

Bottom Line: NK cells resist engraftment of syngeneic and allogeneic bone marrow (BM) cells lacking major histocompatibility (MHC) class I molecules, suggesting a critical role for donor MHC class I molecules in preventing NK cell attack against donor hematopoietic stem and progenitor cells (HSPCs), and their derivatives.In contrast, syngeneic MHC class I KO differentiated hematopoietic cells and allogeneic MHC class I KO HSPCs were rejected in a manner that was significantly inhibited by NK cell depletion.The data indicate that donor MHC class I molecules are required to prevent NK cell-mediated rejection of syngeneic differentiated cells and allogeneic HSPCs, but not of syngeneic HSPCs.

View Article: PubMed Central - PubMed

Affiliation: Columbia Center for Translational Immunology, Department of Medicine, Surgery and Microbiology/Immunology, College of Physicians and Surgeons, Columbia University, New York, New York, United States of America.

ABSTRACT
NK cells resist engraftment of syngeneic and allogeneic bone marrow (BM) cells lacking major histocompatibility (MHC) class I molecules, suggesting a critical role for donor MHC class I molecules in preventing NK cell attack against donor hematopoietic stem and progenitor cells (HSPCs), and their derivatives. However, using high-resolution in vivo imaging, we demonstrated here that syngeneic MHC class I knockout (KO) donor HSPCs persist with the same survival frequencies as wild-type donor HSPCs. In contrast, syngeneic MHC class I KO differentiated hematopoietic cells and allogeneic MHC class I KO HSPCs were rejected in a manner that was significantly inhibited by NK cell depletion. In vivo time-lapse imaging demonstrated that mice receiving allogeneic MHC class I KO HSPCs showed a significant increase in NK cell motility and proliferation as well as frequencies of NK cell contact with and killing of HSPCs as compared to mice receiving wild-type HSPCs. The data indicate that donor MHC class I molecules are required to prevent NK cell-mediated rejection of syngeneic differentiated cells and allogeneic HSPCs, but not of syngeneic HSPCs.

No MeSH data available.


Related in: MedlinePlus