The role of specific IL-27-producing DC subsets on the magnitude of the CD8 T cell response to subunit vaccines

Abstract The generation of long-lasting, adjuvant-elicited cellular immunity is a significant unmet medical need. Specifically, the use of adjuvants to induce clinically relevant CD8 T cells responses would have great utility in chronic infectious diseases and cancer. Our previous data has shown a unique requirement for T cell intrinsic IL-27 signaling in their response to adjuvanted subunit vaccination. Indeed, the magnitude of IL-27p28 production by cDC1s (CD3/B220 −, CD11c +, XCR1 +) actually predicts the magnitude of the CD8 T cell response generated. cDC1s are also required to present subunit vaccine-derived antigens to responding CD8+ T cells. However, whether IL-27 needs to be produced by the same cDC1s presenting antigen, or whether non-antigen presenting APCs can produce IL-27 in trans, for the maximal CD8+ T cell response to subunit vaccination is as of yet unknown. Here, we confirm that IL-27p28 is required for maximal adjuvant-elicited CD8 T cell responses. Furthermore, in mice with Il-27p28 deleted in only CD11c+ cells (IL-27p28 fl/flx CD11c-cre) the CD8 cell response to vaccination phenocopied the defective response seen in mice fully deficient in IL-27p28, EIB3, and IL-27 receptor. Interestingly, the distribution of MPECs (CD127hi) and SLECs (KLRG1 hi, CD127 lo) in these mice as compared to WT (C57BL/6) controls did not vary. Numerous myeloid subsets (cDC2, monocytes) as well as B cells also make IL-27. Utilizing cell-specific cre expression transgenes in conjunction with the floxed IL27p28, we have characterized the cellular requirements for IL-27 in the adjuvant elicited CD8+ T cell response.