The generation of memory CD8 T cells is regulated by intracellular Galectin-3

Abstract

Abstract The ability of tumors to induce immunosuppression and reduce the cytolytic function of tumor-infiltrating lymphocytes (TIL) is a major obstacle to creating effective therapies for cancer patients. The levels of Galectin-3 (Gal3) protein are increased during tumor progression in many cancers. Gal3 induces the polarization of tumor-associated macrophages and plays a role in the survival and metastasis of cancer cells. Gal3 is functional within cells as well as in the extracellular space and recent studies suggest that it has opposing functions in these two compartments. The biology of extracellular Gal3 has been extensively studied, however, the function and mechanisms by which intracellular Gal3 regulates CD8 T cells responses are poorly understood. CD8+ T cells are a critical component of anti-tumor immunity and enhancing their function can promote tumor elimination. Intracellular Gal3 has been suggested to positively regulate CD8+ T cell activation and survival. In the current study, we demonstrate that Gal3-deficient CD8+ T cells has no defect in early activation in vitro. However, Gal3−/− OT-I CD8+ T cells exhibit decreased proliferation, activation, survival and transition to memory in response to cognate antigen in vivo. Together, these data implicate Gal3 as a critical mediator of CD8 T cell survival and memory formation following antigen challenge in vivo.