T cells expanded in presence of IL-15 exhibit elevated cell surface thiols, intracellular glutathione and increased long term survival (48.34)

Abstract Persistence of effector cytotoxic T lymphocytes (CTLs) during an immunological response is critical for successfully controlling a viral infection or tumor growth. Various cytokines are known to play an important part in regulating the immune response. IL-2 and IL-15 possess similar properties, including the ability to induce T cell proliferation. The IL-2 family of cytokines that includes IL-2 and IL-15 are known to function as growth and survival factors for antigen-experienced T cells. Whereas long term IL-2 exposure has been shown to promote apoptosis and limit CD8+ memory T cell survival and proliferation, it is widely believed that IL-15 can inhibit apoptosis and maintains a memory CD8+ T-cell population. Our data show that human T cells and CTLs specific for melanoma reactive antigen Mart-127-35 and influenza matrix protein MP58-66 expanded in vitro in the presence of IL-15 had higher expression of CD56 and increased survival due to higher levels of anti-apoptotic proteins bcl-2, bcl-xl, cell surface thiols, and intracellular glutathione. Our study suggests that increased longevity of CTL cultured in the presence of IL-15 might depend on increased expression of antioxidant proteins and a subset of a highly expressed CD56hi population. Efforts to modulate the redox pathway may increase the T-cell survival without compromising cell functionality and confer therapeutic benefit to T-cell-based immunotherapy protocols.