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KLRG1 signaling induces defective Akt (ser473) phosphorylation and proliferative dysfunction of highly differentiated CD8+ T cells
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| Zeitschriftentitel: | Blood |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , , |
| In: | Blood, 113, 2009, 26, S. 6619-6628 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Society of Hematology
|
| Schlagwörter: |
| author_facet |
Henson, Sian M. Franzese, Ornella Macaulay, Richard Libri, Valentina Azevedo, Rita I. Kiani-Alikhan, Sorena Plunkett, Fiona J. Masters, Joanne E. Jackson, Sarah Griffiths, Stephen J. Pircher, Hans-Peter Soares, Maria V. D. Akbar, Arne N. Henson, Sian M. Franzese, Ornella Macaulay, Richard Libri, Valentina Azevedo, Rita I. Kiani-Alikhan, Sorena Plunkett, Fiona J. Masters, Joanne E. Jackson, Sarah Griffiths, Stephen J. Pircher, Hans-Peter Soares, Maria V. D. Akbar, Arne N. |
|---|---|
| author |
Henson, Sian M. Franzese, Ornella Macaulay, Richard Libri, Valentina Azevedo, Rita I. Kiani-Alikhan, Sorena Plunkett, Fiona J. Masters, Joanne E. Jackson, Sarah Griffiths, Stephen J. Pircher, Hans-Peter Soares, Maria V. D. Akbar, Arne N. |
| spellingShingle |
Henson, Sian M. Franzese, Ornella Macaulay, Richard Libri, Valentina Azevedo, Rita I. Kiani-Alikhan, Sorena Plunkett, Fiona J. Masters, Joanne E. Jackson, Sarah Griffiths, Stephen J. Pircher, Hans-Peter Soares, Maria V. D. Akbar, Arne N. Blood KLRG1 signaling induces defective Akt (ser473) phosphorylation and proliferative dysfunction of highly differentiated CD8+ T cells Cell Biology Hematology Immunology Biochemistry |
| author_sort |
henson, sian m. |
| spelling |
Henson, Sian M. Franzese, Ornella Macaulay, Richard Libri, Valentina Azevedo, Rita I. Kiani-Alikhan, Sorena Plunkett, Fiona J. Masters, Joanne E. Jackson, Sarah Griffiths, Stephen J. Pircher, Hans-Peter Soares, Maria V. D. Akbar, Arne N. 0006-4971 1528-0020 American Society of Hematology Cell Biology Hematology Immunology Biochemistry http://dx.doi.org/10.1182/blood-2009-01-199588 <jats:title>Abstract</jats:title><jats:p>Highly differentiated CD8+CD28−CD27− T cells have short telomeres, defective telomerase activity, and reduced capacity for proliferation, indicating that they are close to replicative senescence. In addition, these cells express increased levels of the senescence-associated inhibitory receptor KLRG1 and have poor capacity for IL-2 synthesis and defective Akt (ser473) phosphorylation after activation. It is not known whether signaling via KLRG1 contributes to any of the attenuated differentiation-related functional changes in CD8+ T cells. To address this, we blocked KLRG1 signaling during T-cell receptor activation using antibodies against its major ligand, E-cadherin. This resulted in a significant enhancement of Akt (ser473) phosphorylation and T-cell receptor–induced proliferative activity of CD8+CD28−CD27− T cells. Furthermore, the increase of proliferation was directly linked to the Akt-mediated induction of cyclin D and E and reduction in the cyclin inhibitor p27 expression. In contrast, the reduced telomerase activity in highly differentiated CD8+CD28−CD27− T cells was not altered by KLRG1 blockade, indicating the involvement of other mechanisms. This is the first demonstration of a functional role for KLRG1 in primary human CD8+ T cells and highlights that certain functional defects that arise during progressive T-cell differentiation toward replicative senescence are maintained actively by inhibitory receptor signaling.</jats:p> KLRG1 signaling induces defective Akt (ser473) phosphorylation and proliferative dysfunction of highly differentiated CD8+ T cells Blood |
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American Society of Hematology, 2009 |
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American Society of Hematology, 2009 |
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| title |
KLRG1 signaling induces defective Akt (ser473) phosphorylation and proliferative dysfunction of highly differentiated CD8+ T cells |
| title_unstemmed |
KLRG1 signaling induces defective Akt (ser473) phosphorylation and proliferative dysfunction of highly differentiated CD8+ T cells |
| title_full |
KLRG1 signaling induces defective Akt (ser473) phosphorylation and proliferative dysfunction of highly differentiated CD8+ T cells |
| title_fullStr |
KLRG1 signaling induces defective Akt (ser473) phosphorylation and proliferative dysfunction of highly differentiated CD8+ T cells |
| title_full_unstemmed |
KLRG1 signaling induces defective Akt (ser473) phosphorylation and proliferative dysfunction of highly differentiated CD8+ T cells |
| title_short |
KLRG1 signaling induces defective Akt (ser473) phosphorylation and proliferative dysfunction of highly differentiated CD8+ T cells |
| title_sort |
klrg1 signaling induces defective akt (ser473) phosphorylation and proliferative dysfunction of highly differentiated cd8+ t cells |
| topic |
Cell Biology Hematology Immunology Biochemistry |
| url |
http://dx.doi.org/10.1182/blood-2009-01-199588 |
| publishDate |
2009 |
| physical |
6619-6628 |
| description |
<jats:title>Abstract</jats:title><jats:p>Highly differentiated CD8+CD28−CD27− T cells have short telomeres, defective telomerase activity, and reduced capacity for proliferation, indicating that they are close to replicative senescence. In addition, these cells express increased levels of the senescence-associated inhibitory receptor KLRG1 and have poor capacity for IL-2 synthesis and defective Akt (ser473) phosphorylation after activation. It is not known whether signaling via KLRG1 contributes to any of the attenuated differentiation-related functional changes in CD8+ T cells. To address this, we blocked KLRG1 signaling during T-cell receptor activation using antibodies against its major ligand, E-cadherin. This resulted in a significant enhancement of Akt (ser473) phosphorylation and T-cell receptor–induced proliferative activity of CD8+CD28−CD27− T cells. Furthermore, the increase of proliferation was directly linked to the Akt-mediated induction of cyclin D and E and reduction in the cyclin inhibitor p27 expression. In contrast, the reduced telomerase activity in highly differentiated CD8+CD28−CD27− T cells was not altered by KLRG1 blockade, indicating the involvement of other mechanisms. This is the first demonstration of a functional role for KLRG1 in primary human CD8+ T cells and highlights that certain functional defects that arise during progressive T-cell differentiation toward replicative senescence are maintained actively by inhibitory receptor signaling.</jats:p> |
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| author | Henson, Sian M., Franzese, Ornella, Macaulay, Richard, Libri, Valentina, Azevedo, Rita I., Kiani-Alikhan, Sorena, Plunkett, Fiona J., Masters, Joanne E., Jackson, Sarah, Griffiths, Stephen J., Pircher, Hans-Peter, Soares, Maria V. D., Akbar, Arne N. |
| author_facet | Henson, Sian M., Franzese, Ornella, Macaulay, Richard, Libri, Valentina, Azevedo, Rita I., Kiani-Alikhan, Sorena, Plunkett, Fiona J., Masters, Joanne E., Jackson, Sarah, Griffiths, Stephen J., Pircher, Hans-Peter, Soares, Maria V. D., Akbar, Arne N., Henson, Sian M., Franzese, Ornella, Macaulay, Richard, Libri, Valentina, Azevedo, Rita I., Kiani-Alikhan, Sorena, Plunkett, Fiona J., Masters, Joanne E., Jackson, Sarah, Griffiths, Stephen J., Pircher, Hans-Peter, Soares, Maria V. D., Akbar, Arne N. |
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| description | <jats:title>Abstract</jats:title><jats:p>Highly differentiated CD8+CD28−CD27− T cells have short telomeres, defective telomerase activity, and reduced capacity for proliferation, indicating that they are close to replicative senescence. In addition, these cells express increased levels of the senescence-associated inhibitory receptor KLRG1 and have poor capacity for IL-2 synthesis and defective Akt (ser473) phosphorylation after activation. It is not known whether signaling via KLRG1 contributes to any of the attenuated differentiation-related functional changes in CD8+ T cells. To address this, we blocked KLRG1 signaling during T-cell receptor activation using antibodies against its major ligand, E-cadherin. This resulted in a significant enhancement of Akt (ser473) phosphorylation and T-cell receptor–induced proliferative activity of CD8+CD28−CD27− T cells. Furthermore, the increase of proliferation was directly linked to the Akt-mediated induction of cyclin D and E and reduction in the cyclin inhibitor p27 expression. In contrast, the reduced telomerase activity in highly differentiated CD8+CD28−CD27− T cells was not altered by KLRG1 blockade, indicating the involvement of other mechanisms. This is the first demonstration of a functional role for KLRG1 in primary human CD8+ T cells and highlights that certain functional defects that arise during progressive T-cell differentiation toward replicative senescence are maintained actively by inhibitory receptor signaling.</jats:p> |
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| imprint | American Society of Hematology, 2009 |
| imprint_str_mv | American Society of Hematology, 2009 |
| institution | DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4 |
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| spelling | Henson, Sian M. Franzese, Ornella Macaulay, Richard Libri, Valentina Azevedo, Rita I. Kiani-Alikhan, Sorena Plunkett, Fiona J. Masters, Joanne E. Jackson, Sarah Griffiths, Stephen J. Pircher, Hans-Peter Soares, Maria V. D. Akbar, Arne N. 0006-4971 1528-0020 American Society of Hematology Cell Biology Hematology Immunology Biochemistry http://dx.doi.org/10.1182/blood-2009-01-199588 <jats:title>Abstract</jats:title><jats:p>Highly differentiated CD8+CD28−CD27− T cells have short telomeres, defective telomerase activity, and reduced capacity for proliferation, indicating that they are close to replicative senescence. In addition, these cells express increased levels of the senescence-associated inhibitory receptor KLRG1 and have poor capacity for IL-2 synthesis and defective Akt (ser473) phosphorylation after activation. It is not known whether signaling via KLRG1 contributes to any of the attenuated differentiation-related functional changes in CD8+ T cells. To address this, we blocked KLRG1 signaling during T-cell receptor activation using antibodies against its major ligand, E-cadherin. This resulted in a significant enhancement of Akt (ser473) phosphorylation and T-cell receptor–induced proliferative activity of CD8+CD28−CD27− T cells. Furthermore, the increase of proliferation was directly linked to the Akt-mediated induction of cyclin D and E and reduction in the cyclin inhibitor p27 expression. In contrast, the reduced telomerase activity in highly differentiated CD8+CD28−CD27− T cells was not altered by KLRG1 blockade, indicating the involvement of other mechanisms. This is the first demonstration of a functional role for KLRG1 in primary human CD8+ T cells and highlights that certain functional defects that arise during progressive T-cell differentiation toward replicative senescence are maintained actively by inhibitory receptor signaling.</jats:p> KLRG1 signaling induces defective Akt (ser473) phosphorylation and proliferative dysfunction of highly differentiated CD8+ T cells Blood |
| spellingShingle | Henson, Sian M., Franzese, Ornella, Macaulay, Richard, Libri, Valentina, Azevedo, Rita I., Kiani-Alikhan, Sorena, Plunkett, Fiona J., Masters, Joanne E., Jackson, Sarah, Griffiths, Stephen J., Pircher, Hans-Peter, Soares, Maria V. D., Akbar, Arne N., Blood, KLRG1 signaling induces defective Akt (ser473) phosphorylation and proliferative dysfunction of highly differentiated CD8+ T cells, Cell Biology, Hematology, Immunology, Biochemistry |
| title | KLRG1 signaling induces defective Akt (ser473) phosphorylation and proliferative dysfunction of highly differentiated CD8+ T cells |
| title_full | KLRG1 signaling induces defective Akt (ser473) phosphorylation and proliferative dysfunction of highly differentiated CD8+ T cells |
| title_fullStr | KLRG1 signaling induces defective Akt (ser473) phosphorylation and proliferative dysfunction of highly differentiated CD8+ T cells |
| title_full_unstemmed | KLRG1 signaling induces defective Akt (ser473) phosphorylation and proliferative dysfunction of highly differentiated CD8+ T cells |
| title_short | KLRG1 signaling induces defective Akt (ser473) phosphorylation and proliferative dysfunction of highly differentiated CD8+ T cells |
| title_sort | klrg1 signaling induces defective akt (ser473) phosphorylation and proliferative dysfunction of highly differentiated cd8+ t cells |
| title_unstemmed | KLRG1 signaling induces defective Akt (ser473) phosphorylation and proliferative dysfunction of highly differentiated CD8+ T cells |
| topic | Cell Biology, Hematology, Immunology, Biochemistry |
| url | http://dx.doi.org/10.1182/blood-2009-01-199588 |