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Immunol."],"abstract":"<jats:p>Viral vectors have emerged as a promising alternative to classical vaccines due to their great potential for induction of a potent cellular and humoral immunity. Cytomegalovirus (CMV) is an attractive vaccine vector due to its large genome with many non-essential immunoregulatory genes that can be easily manipulated to modify the immune response. CMV generates a strong antigen-specific CD8 T cell response with a gradual accumulation of these cells in the process called memory inflation. In our previous work, we have constructed a mouse CMV vector expressing NKG2D ligand RAE-1\u03b3 in place of its viral inhibitor m152 (RAE-1\u03b3MCMV), which proved to be highly attenuated<jats:italic>in vivo<\/jats:italic>. Despite attenuation, RAE-1\u03b3MCMV induced a substantially stronger CD8 T cell response to vectored antigen than the control vector and provided superior protection against bacterial and tumor challenge. In the present study, we confirmed the enhanced protective capacity of RAE-1\u03b3MCMV as a tumor vaccine vector and determined the phenotypical and functional characteristics of memory CD8 T cells induced by the RAE-1\u03b3 expressing MCMV. RNAseq data revealed higher transcription of numerous genes associated with effector-like CD8 T cell phenotype in RAE-1\u03b3MCMV immunized mice. CD8 T cells primed with RAE-1\u03b3MCMV were enriched in TCF1 negative population, with higher expression of KLRG1 and lower expression of CD127, CD27, and Eomes. These phenotypical differences were associated with distinct functional features as cells primed with RAE-1\u03b3MCMV showed inferior cytokine-producing abilities but comparable cytotoxic potential. After adoptive transfer into naive hosts, OT-1 cells induced with both RAE-1\u03b3MCMV and the control vector were equally efficient in rejecting established tumors, suggesting the context of latent infection and cell numbers as important determinants of enhanced anti-tumor response following RAE-1\u03b3MCMV vaccination. Overall, our results shed new light on the phenotypical and functional distinctness of memory CD8 T cells induced with CMV vector expressing cellular ligand for the NKG2D receptor.<\/jats:p>","DOI":"10.3389\/fimmu.2021.681380","type":"journal-article","created":{"date-parts":[[2021,6,3]],"date-time":"2021-06-03T23:50:56Z","timestamp":1622764256000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Memory CD8 T Cells Generated by Cytomegalovirus Vaccine Vector Expressing NKG2D Ligand Have Effector-Like Phenotype and Distinct Functional Features"],"prefix":"10.3389","volume":"12","author":[{"given":"Marko","family":"\u0160usti\u0107","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maja","family":"Cokari\u0107 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