Submitted May 5, 2008
Accepted April 10, 2009
IL-7 adjuvant treatment enhances long-term tumor antigen-specific CD8+ T cell responses following immunization with recombinant lentivectors
Sara Colombetti*, Frederic Levy, and Laurence Chapatte
Ludwig Institute for Cancer Research-Lausanne Branch, University of Lausanne, Epalinges, Switzerland
* Corresponding author; email: sara.colombetti{at}licr.unil.ch.
Immunization with recombinant lentivectors (rec. lv) elicits higher frequencies of tumor antigen-specific memory CD8+ T cells than peptide-based vaccines. This finding correlates with our observation that, upon rec. lv immunization, a higher fraction of antigen-specific effector CD8+ T cells does not down-regulate the expression of the survival/memory marker IL-7R
. Here we show that, surprisingly, higher expression of IL-7R on rec.lv-induced effector CD8+ T cells doesn't result in the up-regulation of survival molecules, such as Bcl-2. We thus hypothesized that physiological 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 up-regulation 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 rec. lv 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 at the surface of effector CD8+ T cells.
