IL-7 adjuvant treatment enhances long-term tumor antigen-specific CD8+ T-cell responses after immunization with recombinant lentivector

Immunization with recombinant lentivector elicits higher frequencies of tumor antigen-specific memory CD8(+) T cells than peptide-based vaccines. This finding correlates with our observation that, upon recombinant lentivector immunization, a higher fraction of antigen-specific effector CD8(+)T cells does not down-regulate the expression of the survival/memory marker interleukin-7 receptor alpha chain (IL-7R alpha). Here we show that, surprisingly, higher expression of IL-7R alpha on recombinant lentivector-induced effector CD8(+) T cells does not result in the up-regulation of survival molecules, such as Bcl-2. We thus hypothesized that physiologic levels of IL-7 might be limiting in vivo for delivering survival signals to the expanding population of effector cells. To test this hypothesis, we administered recombinant IL-7 during the effector phase of the response. We observed an upregulation of Bcl-2 and a strong expansion of antigen-specific effector CD8(+) T cells, and of naive CD8(+) T cells. Strikingly, IL-7 treatment elicited also a significant increase in the number of antigen-specific memory CD8(+) T cells in recombinant lentivector-immunized mice, but not in peptide-immunized mice. Altogether, these data show that IL-7 adjuvant treatment can enhance long-term antigen-specific CD8(+) T-cell responses. However, its efficacy depends on the expression of IL-7R alpha at the surface of effector CD8(+) T cells. (Blood. 2009; 113: 6629-6637)