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Blood, 25 June 2009, Vol. 113, No. 26, pp. 6629-6637.
Prepublished online as a Blood First Edition Paper on April 21, 2009; DOI 10.1182/blood-2008-05-155309.


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IMMUNOBIOLOGY

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

Sara Colombetti1, Frédéric Lévy1, and Laurence Chapatte1

1 Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland

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 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 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.


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