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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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Lymph node and splenic CD44+ T cells after arterial injury in WT mice.Representative scatter plots of lymph node (LN) and spleen cells collected at various times after injury and characterized using CD44 gated on CD4 (A) or CD8b (B). Cells were collected from uninjured (UI) mice, or 7 days (D7) and 21 days (D21) after arterial injury. Sham mice correspond to 7 days after sham surgery. Percentage of cells is indicated on the top right corner of each graph.
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pone-0020214-g001: Lymph node and splenic CD44+ T cells after arterial injury in WT mice.Representative scatter plots of lymph node (LN) and spleen cells collected at various times after injury and characterized using CD44 gated on CD4 (A) or CD8b (B). Cells were collected from uninjured (UI) mice, or 7 days (D7) and 21 days (D21) after arterial injury. Sham mice correspond to 7 days after sham surgery. Percentage of cells is indicated on the top right corner of each graph.

Mentions: There was no significant increase in CD4+CD69+ T cells in the lymph nodes and spleens after injury (not shown), as previously reported [10]. CD4+CD44hi T cells in the lymph nodes (Fig. 1A, top panel) and spleen (Fig. 1A, bottom panel) of WT mice significantly increased 7 days after injury. Twenty-one days after injury, CD4+CD44hi cells decreased back to uninjured levels (Fig. 1A and Table 1). CD4+CD25+ and CD4+CD28+ T cells did not significantly change after injury (Table 1). The sham group did not have significant changes in CD4+ T cells (Fig. 1A and Table 1).


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)

Lymph node and splenic CD44+ T cells after arterial injury in WT mice.Representative scatter plots of lymph node (LN) and spleen cells collected at various times after injury and characterized using CD44 gated on CD4 (A) or CD8b (B). Cells were collected from uninjured (UI) mice, or 7 days (D7) and 21 days (D21) after arterial injury. Sham mice correspond to 7 days after sham surgery. Percentage of cells is indicated on the top right corner of each graph.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0020214-g001: Lymph node and splenic CD44+ T cells after arterial injury in WT mice.Representative scatter plots of lymph node (LN) and spleen cells collected at various times after injury and characterized using CD44 gated on CD4 (A) or CD8b (B). Cells were collected from uninjured (UI) mice, or 7 days (D7) and 21 days (D21) after arterial injury. Sham mice correspond to 7 days after sham surgery. Percentage of cells is indicated on the top right corner of each graph.
Mentions: There was no significant increase in CD4+CD69+ T cells in the lymph nodes and spleens after injury (not shown), as previously reported [10]. CD4+CD44hi T cells in the lymph nodes (Fig. 1A, top panel) and spleen (Fig. 1A, bottom panel) of WT mice significantly increased 7 days after injury. Twenty-one days after injury, CD4+CD44hi cells decreased back to uninjured levels (Fig. 1A and Table 1). CD4+CD25+ and CD4+CD28+ T cells did not significantly change after injury (Table 1). The sham group did not have significant changes in CD4+ T cells (Fig. 1A and Table 1).

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