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Cytomegalovirus (CMV) and non-replicating adenoviral vectors can induce expanded, sustained effector-memory CD8+ T-cell responses, termed "memory inflation". During murine CMV (MCMV) infection, CD4+ Tcells maintain inflationary virus-specific CD8+ T-cell responses via IL-2 but not IL-21. Adenovirus vector vaccination can induce phenotypically, functionally and transcriptionally similar inflationary responses, but it is not known how IL-21 influences the inflating memory response to adenoviral vaccination. Here, we show that IL-21 is an absolute requirement for induction and maintenance of vaccine-derived inflationary CD8+ T-cell responses. These data indicate that the induction pathway of inflationary Ad-LacZ T-cells is distinct from inflationary MCMV-specific T-cells and is highly dependent on IL-21. Our observations highlight a fundamental difference in the mechanism by which adenovirus vectors and MCMV drive inflationary T-cell responses.

Original publication

DOI

10.1016/j.vaccine.2018.09.061

Type

Journal article

Journal

Vaccine

Publication Date

12/11/2018

Volume

36

Pages

7011 - 7016

Keywords

Adenovirus vectors, Memory T cells, Memory inflation, Adenovirus Vaccines, Animals, CD8-Positive T-Lymphocytes, Immunologic Memory, Interleukins, Mice, Inbred C57BL, Mice, Transgenic