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Enhanced neointima formation following arterial injury in immune deficient Rag-1-/- mice is attenuated by adoptive transfer of CD8 T cells.

Dimayuga PC, Chyu KY, Kirzner J, Yano J, Zhao X, Zhou J, Shah PK, Cercek B - PLoS ONE (2011)

Bottom Line: Splenic CD8(+)CD25(+) T cells and CD8(+)CD28(+) T cells, but not CD4(+)CD25(+) and CD4(+)CD28(+) T cells, were also significantly increased.CD4(+) T cell transfer did not reduce neointima formation.The study shows that although both CD8(+) T cells and CD4(+) T cells are activated in response to arterial injury, adoptive cell transfer identifies CD8(+) T cells as the specific and selective cell type involved in inhibiting neointima formation.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiology, Oppenheimer Atherosclerosis Research Center, Cedars-Sinai Heart Institute, Los Angeles, California, United States of America. DimayugaP@cshs.org

ABSTRACT
T cells modulate neointima formation after arterial injury but the specific T cell population that is activated in response to arterial injury remains unknown. The objective of the study was to identify the T cell populations that are activated and modulate neointimal thickening after arterial injury in mice. Arterial injury in wild type C57Bl6 mice resulted in T cell activation characterized by increased CD4(+)CD44(hi) and CD8(+)CD44(hi) T cells in the lymph nodes and spleens. Splenic CD8(+)CD25(+) T cells and CD8(+)CD28(+) T cells, but not CD4(+)CD25(+) and CD4(+)CD28(+) T cells, were also significantly increased. Adoptive cell transfer of CD4(+) or CD8(+) T cells from donor CD8-/- or CD4-/- mice, respectively, to immune-deficient Rag-1-/- mice was performed to determine the T cell subtype that inhibits neointima formation after arterial injury. Rag-1-/- mice that received CD8(+) T cells had significantly reduced neointima formation compared with Rag-1-/- mice without cell transfer. CD4(+) T cell transfer did not reduce neointima formation. CD8(+) T cells from CD4-/- mice had cytotoxic activity against syngeneic smooth muscle cells in vitro. The study shows that although both CD8(+) T cells and CD4(+) T cells are activated in response to arterial injury, adoptive cell transfer identifies CD8(+) T cells as the specific and selective cell type involved in inhibiting neointima formation.

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Characterization of cells transferred to recipient Rag-1−/− mice.T cells enriched from pooled spleens of CD4−/− mice (Donor CD8+) were used for flow cytometric analysis and compared with T cells enriched from spleens of CD8+ T cell recipient Rag-1−/− mice 48 hours after cell transfer without injury (UI), and 21 days after injury (D21). Representative flow cytometric analysis of CD62L or CD44 gated on CD8b+ cells from donor mice (A). CD8b+CD62L+ (B) and CD8b+CD44hi (C) cells T cells were compared between Donors (N = 3), UI recipients (N = 4) and D21 recipients (N = 4). *P<0.05 vs Donors and UI; †P<0.01 vs Donors and UI.
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pone-0020214-g007: Characterization of cells transferred to recipient Rag-1−/− mice.T cells enriched from pooled spleens of CD4−/− mice (Donor CD8+) were used for flow cytometric analysis and compared with T cells enriched from spleens of CD8+ T cell recipient Rag-1−/− mice 48 hours after cell transfer without injury (UI), and 21 days after injury (D21). Representative flow cytometric analysis of CD62L or CD44 gated on CD8b+ cells from donor mice (A). CD8b+CD62L+ (B) and CD8b+CD44hi (C) cells T cells were compared between Donors (N = 3), UI recipients (N = 4) and D21 recipients (N = 4). *P<0.05 vs Donors and UI; †P<0.01 vs Donors and UI.

Mentions: Spleen cells were collected from donor mice (designated as Donor CD8+), uninjured recipient mice 48 hours after T cell transfer (UI), or recipient mice 21 days after injury (D21). Donor cells were aliquoted from the pooled donor spleens before adoptive transfer. Spleens from 2–3 uninjured recipient mice were pooled due to the small size of spleens, whereas individual spleens were used for the D21 time point. Cells were enriched for T cells and flow cytometric analysis was performed. CD8b+CD62L+ T cells were unchanged in uninjured recipient mice compared with donor T cells but were significantly reduced 21 days after injury (Fig. 7B). CD8+CD44hi T cells increased in uninjured mice and significantly increased further D21 after injury (Fig. 7C).


Enhanced neointima formation following arterial injury in immune deficient Rag-1-/- mice is attenuated by adoptive transfer of CD8 T cells.

Dimayuga PC, Chyu KY, Kirzner J, Yano J, Zhao X, Zhou J, Shah PK, Cercek B - PLoS ONE (2011)

Characterization of cells transferred to recipient Rag-1−/− mice.T cells enriched from pooled spleens of CD4−/− mice (Donor CD8+) were used for flow cytometric analysis and compared with T cells enriched from spleens of CD8+ T cell recipient Rag-1−/− mice 48 hours after cell transfer without injury (UI), and 21 days after injury (D21). Representative flow cytometric analysis of CD62L or CD44 gated on CD8b+ cells from donor mice (A). CD8b+CD62L+ (B) and CD8b+CD44hi (C) cells T cells were compared between Donors (N = 3), UI recipients (N = 4) and D21 recipients (N = 4). *P<0.05 vs Donors and UI; †P<0.01 vs Donors and UI.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3101237&req=5

pone-0020214-g007: Characterization of cells transferred to recipient Rag-1−/− mice.T cells enriched from pooled spleens of CD4−/− mice (Donor CD8+) were used for flow cytometric analysis and compared with T cells enriched from spleens of CD8+ T cell recipient Rag-1−/− mice 48 hours after cell transfer without injury (UI), and 21 days after injury (D21). Representative flow cytometric analysis of CD62L or CD44 gated on CD8b+ cells from donor mice (A). CD8b+CD62L+ (B) and CD8b+CD44hi (C) cells T cells were compared between Donors (N = 3), UI recipients (N = 4) and D21 recipients (N = 4). *P<0.05 vs Donors and UI; †P<0.01 vs Donors and UI.
Mentions: Spleen cells were collected from donor mice (designated as Donor CD8+), uninjured recipient mice 48 hours after T cell transfer (UI), or recipient mice 21 days after injury (D21). Donor cells were aliquoted from the pooled donor spleens before adoptive transfer. Spleens from 2–3 uninjured recipient mice were pooled due to the small size of spleens, whereas individual spleens were used for the D21 time point. Cells were enriched for T cells and flow cytometric analysis was performed. CD8b+CD62L+ T cells were unchanged in uninjured recipient mice compared with donor T cells but were significantly reduced 21 days after injury (Fig. 7B). CD8+CD44hi T cells increased in uninjured mice and significantly increased further D21 after injury (Fig. 7C).

Bottom Line: Splenic CD8(+)CD25(+) T cells and CD8(+)CD28(+) T cells, but not CD4(+)CD25(+) and CD4(+)CD28(+) T cells, were also significantly increased.CD4(+) T cell transfer did not reduce neointima formation.The study shows that although both CD8(+) T cells and CD4(+) T cells are activated in response to arterial injury, adoptive cell transfer identifies CD8(+) T cells as the specific and selective cell type involved in inhibiting neointima formation.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiology, Oppenheimer Atherosclerosis Research Center, Cedars-Sinai Heart Institute, Los Angeles, California, United States of America. DimayugaP@cshs.org

ABSTRACT
T cells modulate neointima formation after arterial injury but the specific T cell population that is activated in response to arterial injury remains unknown. The objective of the study was to identify the T cell populations that are activated and modulate neointimal thickening after arterial injury in mice. Arterial injury in wild type C57Bl6 mice resulted in T cell activation characterized by increased CD4(+)CD44(hi) and CD8(+)CD44(hi) T cells in the lymph nodes and spleens. Splenic CD8(+)CD25(+) T cells and CD8(+)CD28(+) T cells, but not CD4(+)CD25(+) and CD4(+)CD28(+) T cells, were also significantly increased. Adoptive cell transfer of CD4(+) or CD8(+) T cells from donor CD8-/- or CD4-/- mice, respectively, to immune-deficient Rag-1-/- mice was performed to determine the T cell subtype that inhibits neointima formation after arterial injury. Rag-1-/- mice that received CD8(+) T cells had significantly reduced neointima formation compared with Rag-1-/- mice without cell transfer. CD4(+) T cell transfer did not reduce neointima formation. CD8(+) T cells from CD4-/- mice had cytotoxic activity against syngeneic smooth muscle cells in vitro. The study shows that although both CD8(+) T cells and CD4(+) T cells are activated in response to arterial injury, adoptive cell transfer identifies CD8(+) T cells as the specific and selective cell type involved in inhibiting neointima formation.

Show MeSH
Related in: MedlinePlus