IL-21 enhances and sustains CD8+ T cell responses to achieve durable tumor immunity: comparative evaluation of IL-2, IL-15, and IL-21.
Cytokines that use the common receptor gamma-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.
Moroz
Adrianna
A
Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Eppolito
Cheryl
C
Li
Qingsheng
Q
Tao
Jianming
J
Clegg
Christopher H
CH
Shrikant
Protul A
PA
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D007109:Immunity / Q000276:immunology* / Q000502:physiology; D019409:Interleukin-15 / Q000502:physiology*; D007376:Interleukin-2 / Q000502:physiology*; D007378:Interleukins / Q000502:physiology*; D051379:Mice; D009369:Neoplasms / Q000276:immunology*; D000098546:Interleukin-21
D019409:Interleukin-15; D007376:Interleukin-2; D007378:Interleukins; D000098546:Interleukin-21