TY - JOUR
T1 - IL-21 enhances and sustains CD8+ T cell responses to achieve durable tumor immunity
T2 - Comparative evaluation of IL-2, IL-15, and IL-21
AU - Moroz, Adrianna
AU - Eppolito, Cheryl
AU - Li, Qingsheng
AU - Tao, Jianming
AU - Clegg, Christopher H.
AU - Shrikant, Protul A.
PY - 2004/7/15
Y1 - 2004/7/15
N2 - Cytokines that use the common receptor γ-chain for regulating CD8+ T cell responses to Ag include IL-2, IL-15, and the recently identified IL-21. The ability of these cytokines to regulate antitumor activity in mice has generated considerable interest in understanding their mode of action. In this study we compare the abilities of IL-2, IL-15, and IL-21 to stimulate immunity against tumors in a syngeneic thymoma model. Durable cures were only achieved in IL-21-treated mice. By monitoring both endogenous and adoptively transferred tumor Ag-specific CD8+ T cells, it was determined that IL-21 activities overlap with those of IL-2 and IL-15. Similar to IL-2, IL-21 enhanced Ag activation and clonal expansion. However, unlike IL-2 treatment, which induces activation-induced cell death, IL-21 sustained CD8+ T cell numbers long term as a result of increased survival, an effect often attributed to IL-15. These findings indicate that the mechanisms used by IL-21 to promote CD8+ T cell responses offer unique opportunities for its use in malignant diseases and infections.
AB - Cytokines that use the common receptor γ-chain for regulating CD8+ T cell responses to Ag include IL-2, IL-15, and the recently identified IL-21. The ability of these cytokines to regulate antitumor activity in mice has generated considerable interest in understanding their mode of action. In this study we compare the abilities of IL-2, IL-15, and IL-21 to stimulate immunity against tumors in a syngeneic thymoma model. Durable cures were only achieved in IL-21-treated mice. By monitoring both endogenous and adoptively transferred tumor Ag-specific CD8+ T cells, it was determined that IL-21 activities overlap with those of IL-2 and IL-15. Similar to IL-2, IL-21 enhanced Ag activation and clonal expansion. However, unlike IL-2 treatment, which induces activation-induced cell death, IL-21 sustained CD8+ T cell numbers long term as a result of increased survival, an effect often attributed to IL-15. These findings indicate that the mechanisms used by IL-21 to promote CD8+ T cell responses offer unique opportunities for its use in malignant diseases and infections.
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U2 - 10.4049/jimmunol.173.2.900
DO - 10.4049/jimmunol.173.2.900
M3 - Article
C2 - 15240677
AN - SCOPUS:2542595794
SN - 0022-1767
VL - 173
SP - 900
EP - 909
JO - Journal of Immunology
JF - Journal of Immunology
IS - 2
ER -