Abstract
The role of PI-3K in leukocyte function has been studied extensively. However, the specific role of the p110γ isoform of PI- 3K in CD4 T lymphocyte function has yet to be defined explicitly. In this study, we report that although p110γ does not regulate antigen-dependent CD4 T cell activation and proliferation, it plays a crucial role in regulating CD4 effector T cell migration. Naïve p110γ-/- CD4 lymphocytes are phenotypically identical to their wildtype (WT) counterparts and do not exhibit any defects in TCR-mediated calcium mobilization or Erk activation. In addition, p110γ-deficient CD4 OT.II T cells become activated and proliferate comparably with WT cells in response to antigen in vivo. Interestingly, however, antigen-experienced, p110γ-deficient CD4 OT.II lymphocytes exhibit dramatic defects in their ability to traffic to peripheral inflammatory sites in vivo. Although antigen-activated, p110γ-deficient CD4 T cells express P-selectin ligand, β2 integrin, β1 integrin, CCR4, CXCR5, and CCR7 comparably with WT cells, they exhibit impaired Factin polarization and migration in response to stimulation ex vivo with the CCR4 ligand CCL22. These findings suggest that p110γ regulates the migration of antigen-experienced effector CD4 T lymphocytes into inflammatory sites during adaptive immune responses in vivo.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 814-823 |
| Number of pages | 10 |
| Journal | Journal of Leukocyte Biology |
| Volume | 84 |
| Issue number | 3 |
| DOIs | |
| State | Published - Sep 1 2008 |
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Keywords
- Activation
- Chemokines
- Inflammation
- Leukocyte
- Trafficking
Cite this
The p110γ isoform of phosphatidylinositol 3-kinase regulates migration of effector CD4 T lymphocytes into peripheral inflammatory sites. / Thomas, Molly S.; Mitchell, Jason S; Denucci, Christopher C.; Martin, Amanda L.; Shimizu, Yoji.
In: Journal of Leukocyte Biology, Vol. 84, No. 3, 01.09.2008, p. 814-823.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The p110γ isoform of phosphatidylinositol 3-kinase regulates migration of effector CD4 T lymphocytes into peripheral inflammatory sites
AU - Thomas, Molly S.
AU - Mitchell, Jason S
AU - Denucci, Christopher C.
AU - Martin, Amanda L.
AU - Shimizu, Yoji
PY - 2008/9/1
Y1 - 2008/9/1
N2 - The role of PI-3K in leukocyte function has been studied extensively. However, the specific role of the p110γ isoform of PI- 3K in CD4 T lymphocyte function has yet to be defined explicitly. In this study, we report that although p110γ does not regulate antigen-dependent CD4 T cell activation and proliferation, it plays a crucial role in regulating CD4 effector T cell migration. Naïve p110γ-/- CD4 lymphocytes are phenotypically identical to their wildtype (WT) counterparts and do not exhibit any defects in TCR-mediated calcium mobilization or Erk activation. In addition, p110γ-deficient CD4 OT.II T cells become activated and proliferate comparably with WT cells in response to antigen in vivo. Interestingly, however, antigen-experienced, p110γ-deficient CD4 OT.II lymphocytes exhibit dramatic defects in their ability to traffic to peripheral inflammatory sites in vivo. Although antigen-activated, p110γ-deficient CD4 T cells express P-selectin ligand, β2 integrin, β1 integrin, CCR4, CXCR5, and CCR7 comparably with WT cells, they exhibit impaired Factin polarization and migration in response to stimulation ex vivo with the CCR4 ligand CCL22. These findings suggest that p110γ regulates the migration of antigen-experienced effector CD4 T lymphocytes into inflammatory sites during adaptive immune responses in vivo.
AB - The role of PI-3K in leukocyte function has been studied extensively. However, the specific role of the p110γ isoform of PI- 3K in CD4 T lymphocyte function has yet to be defined explicitly. In this study, we report that although p110γ does not regulate antigen-dependent CD4 T cell activation and proliferation, it plays a crucial role in regulating CD4 effector T cell migration. Naïve p110γ-/- CD4 lymphocytes are phenotypically identical to their wildtype (WT) counterparts and do not exhibit any defects in TCR-mediated calcium mobilization or Erk activation. In addition, p110γ-deficient CD4 OT.II T cells become activated and proliferate comparably with WT cells in response to antigen in vivo. Interestingly, however, antigen-experienced, p110γ-deficient CD4 OT.II lymphocytes exhibit dramatic defects in their ability to traffic to peripheral inflammatory sites in vivo. Although antigen-activated, p110γ-deficient CD4 T cells express P-selectin ligand, β2 integrin, β1 integrin, CCR4, CXCR5, and CCR7 comparably with WT cells, they exhibit impaired Factin polarization and migration in response to stimulation ex vivo with the CCR4 ligand CCL22. These findings suggest that p110γ regulates the migration of antigen-experienced effector CD4 T lymphocytes into inflammatory sites during adaptive immune responses in vivo.
KW - Activation
KW - Chemokines
KW - Inflammation
KW - Leukocyte
KW - Trafficking
UR - http://www.scopus.com/inward/record.url?scp=50849122062&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=50849122062&partnerID=8YFLogxK
U2 - 10.1189/jlb.0807561
DO - 10.1189/jlb.0807561
M3 - Article
C2 - 18523230
AN - SCOPUS:50849122062
VL - 84
SP - 814
EP - 823
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
SN - 0741-5400
IS - 3
ER -