TY - JOUR
T1 - TGF-β1 attenuates the acquisition and expression of effector function by tumor antigen-specific human memory CD8 T cells
AU - Ahmadzadeh, Mojgan
AU - Rosenberg, Steven A.
PY - 2005/5/1
Y1 - 2005/5/1
N2 - TGF-β1 is a potent immunoregulatory cytokine. However, its impact on the generation and effector function of Ag-specific human effector memory CD8 T cells had not been evaluated. Using Ag-specific CD8 T cells derived from melanoma patients immunized with the gp100 melanoma Ag, we demonstrate that the addition of TGF-β1 to the initial Ag activation cultures attenuated the gain of effector function by Ag-specific memory CD8 T cells while the phenotypic changes associated with activation and differentiation into effector memory were comparable to control cultures. These activated memory CD8 T cells consistently expressed lower mRNA levels for T-bet, suggesting a mechanism for TGF-β1-mediated suppression of gain of effector function in memory T cells. Moreover, TGF-β1 induced a modest expression of CCR7 on Ag-activated memory CD8 T cells. TGF-β1 also suppressed cytokine secretion by Ag-specific effector memory CD8 T cells, as well as melanoma-reactive tumor-infiltrating lymphocytes and CD8 T cell clones. These results demonstrate that TGF-β1 suppresses not only the acquisition but also expression of effector function on human memory CD8 T cells and tumor-infiltrating lymphocytes reactive against melanoma, suggesting that TGF-β1-mediated suppression can hinder the therapeutic benefits of vaccination, as well as immunotherapy in cancer patients.
AB - TGF-β1 is a potent immunoregulatory cytokine. However, its impact on the generation and effector function of Ag-specific human effector memory CD8 T cells had not been evaluated. Using Ag-specific CD8 T cells derived from melanoma patients immunized with the gp100 melanoma Ag, we demonstrate that the addition of TGF-β1 to the initial Ag activation cultures attenuated the gain of effector function by Ag-specific memory CD8 T cells while the phenotypic changes associated with activation and differentiation into effector memory were comparable to control cultures. These activated memory CD8 T cells consistently expressed lower mRNA levels for T-bet, suggesting a mechanism for TGF-β1-mediated suppression of gain of effector function in memory T cells. Moreover, TGF-β1 induced a modest expression of CCR7 on Ag-activated memory CD8 T cells. TGF-β1 also suppressed cytokine secretion by Ag-specific effector memory CD8 T cells, as well as melanoma-reactive tumor-infiltrating lymphocytes and CD8 T cell clones. These results demonstrate that TGF-β1 suppresses not only the acquisition but also expression of effector function on human memory CD8 T cells and tumor-infiltrating lymphocytes reactive against melanoma, suggesting that TGF-β1-mediated suppression can hinder the therapeutic benefits of vaccination, as well as immunotherapy in cancer patients.
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U2 - 10.4049/jimmunol.174.9.5215
DO - 10.4049/jimmunol.174.9.5215
M3 - Article
C2 - 15843517
AN - SCOPUS:17844402285
SN - 0022-1767
VL - 174
SP - 5215
EP - 5223
JO - Journal of Immunology
JF - Journal of Immunology
IS - 9
ER -