Granzyme B Contributes to the Optimal Graft-Versus-Tumor Effect Mediated by Conventional CD4+ T Cells
(2016) In Journal of immunology research and therapy 1(1). p.22-28- Abstract
Granzyme B (GzmB) is a key cytotoxic molecule utilized by T cells to kill pathogen-infected cells or transformed tumor cells. Previous studies using allogeneic hematopoietic cell transplantation (allo-HCT) murine models showed that GzmB is required for CD8+ T cells to cause graft-versus-host disease (GVHD). However, our recent study demonstrated that GzmB-mediated damage of CD8+ T cells diminished their graft-versus-tumor (GVT) activity. In this study, we examined the role of GzmB in GVT effect mediated by conventional CD4+CD25- T cells (CD4+ Tcon). GzmB-/-CD4+ Tcon cells exhibited decreased GVT activity compared to wild-type (WT) CD4+ Tcon cells, suggesting that GzmB is required for the optimal GVT activity of CD4+ Tcon cells. On the... (More)
Granzyme B (GzmB) is a key cytotoxic molecule utilized by T cells to kill pathogen-infected cells or transformed tumor cells. Previous studies using allogeneic hematopoietic cell transplantation (allo-HCT) murine models showed that GzmB is required for CD8+ T cells to cause graft-versus-host disease (GVHD). However, our recent study demonstrated that GzmB-mediated damage of CD8+ T cells diminished their graft-versus-tumor (GVT) activity. In this study, we examined the role of GzmB in GVT effect mediated by conventional CD4+CD25- T cells (CD4+ Tcon). GzmB-/-CD4+ Tcon cells exhibited decreased GVT activity compared to wild-type (WT) CD4+ Tcon cells, suggesting that GzmB is required for the optimal GVT activity of CD4+ Tcon cells. On the other hand, GzmB-/- CD4+CD25+ regulatory T cells were as suppressive as WT regulatory T cells in suppressing GVT activity, which is consistent with our previous report showing that GzmB is not required for regulatory T cell-mediated suppression of GVHD. These results demonstrate that GzmB causes opposite impacts on GVT effect mediated by CD4+CD25- versus CD8+ T cells. Interestingly, GzmB-/- total T cells exhibited GVT activity equivalent to that of WT total T cells, suggesting that the opposite impacts of GzmB on the GVT effect of CD4+CD25- versus CD8+ T cells may neutralize each other, which can only be observed when an individual T cell subset is examined. Importantly, these differential roles suggest that targeting GzmB in selective T cell subsets may have the potential to enhance the beneficial GVT effect.
(Less)
- author
- Du, Wei ; Leigh, Nicholas D LU ; Bian, Guanglin ; Alqassim, Emad ; O'Neill, Rachel E ; Mei, Lin ; Qiu, Jingxin ; Liu, Hong ; McCarthy, Philip L and Cao, Xuefang
- publishing date
- 2016-04-30
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of immunology research and therapy
- volume
- 1
- issue
- 1
- pages
- 22 - 28
- publisher
- Hindawi Limited
- external identifiers
-
- pmid:27774524
- ISSN
- 2472-727X
- language
- English
- LU publication?
- no
- id
- 310f68b6-41a8-4a17-a156-d974ddd14bf9
- date added to LUP
- 2020-04-28 00:11:20
- date last changed
- 2020-04-28 14:11:39
@article{310f68b6-41a8-4a17-a156-d974ddd14bf9, abstract = {{<p>Granzyme B (GzmB) is a key cytotoxic molecule utilized by T cells to kill pathogen-infected cells or transformed tumor cells. Previous studies using allogeneic hematopoietic cell transplantation (allo-HCT) murine models showed that GzmB is required for CD8+ T cells to cause graft-versus-host disease (GVHD). However, our recent study demonstrated that GzmB-mediated damage of CD8+ T cells diminished their graft-versus-tumor (GVT) activity. In this study, we examined the role of GzmB in GVT effect mediated by conventional CD4+CD25- T cells (CD4+ Tcon). GzmB-/-CD4+ Tcon cells exhibited decreased GVT activity compared to wild-type (WT) CD4+ Tcon cells, suggesting that GzmB is required for the optimal GVT activity of CD4+ Tcon cells. On the other hand, GzmB-/- CD4+CD25+ regulatory T cells were as suppressive as WT regulatory T cells in suppressing GVT activity, which is consistent with our previous report showing that GzmB is not required for regulatory T cell-mediated suppression of GVHD. These results demonstrate that GzmB causes opposite impacts on GVT effect mediated by CD4+CD25- versus CD8+ T cells. Interestingly, GzmB-/- total T cells exhibited GVT activity equivalent to that of WT total T cells, suggesting that the opposite impacts of GzmB on the GVT effect of CD4+CD25- versus CD8+ T cells may neutralize each other, which can only be observed when an individual T cell subset is examined. Importantly, these differential roles suggest that targeting GzmB in selective T cell subsets may have the potential to enhance the beneficial GVT effect.</p>}}, author = {{Du, Wei and Leigh, Nicholas D and Bian, Guanglin and Alqassim, Emad and O'Neill, Rachel E and Mei, Lin and Qiu, Jingxin and Liu, Hong and McCarthy, Philip L and Cao, Xuefang}}, issn = {{2472-727X}}, language = {{eng}}, month = {{04}}, number = {{1}}, pages = {{22--28}}, publisher = {{Hindawi Limited}}, series = {{Journal of immunology research and therapy}}, title = {{Granzyme B Contributes to the Optimal Graft-Versus-Tumor Effect Mediated by Conventional CD4+ T Cells}}, url = {{https://lup.lub.lu.se/search/files/78925314/2016_Du_JIRT.pdf}}, volume = {{1}}, year = {{2016}}, }