In Vitro-Generated Tc17 Cells Present a Memory Phenotype and Serve As a Reservoir of Tc1 Cells In Vivo

Abstract

Memory CD8+ T cells are ideal candidates for cancer immunotherapy because they can mediate long-term protection against tumors. However, the therapeutic potential of different in vitro-generated CD8+ T cell effector subsets to persist and become memory cells has not been fully characterized. Type 1 CD8+ T (Tc1) cells produce interferon-γ and are endowed with high cytotoxic capacity, whereas IL-17-producing CD8+ T (Tc17) cells are less cytotoxic but display enhanced self-renewal capacity. We sought to evaluate the functional properties of in vitro-generated Tc17 cells and elucidate their potential to become long lasting memory cells. Our results show that in vitro-generated Tc17 cells display a greater in vivo persistence and expansion in response to secondary antigen stimulation compared to Tc1 cells. When transferred into recipient mice, Tc17 cells persist in secondary lymphoid organs, present a recirculation behavior consistent with central memory T cells, and can shift to a Tc1 phenotype. Accordingly, Tc17 cells are endowed with a higher mitochondrial spare respiratory capacity than Tc1 cells and express higher levels of memory-related molecules than Tc1 cells. Together, these results demonstrate that in vitro-generated Tc17 cells acquire a central memory program and provide a lasting reservoir of Tc1 cells in vivo, thus supporting the use of Tc17 lymphocytes in the design of novel and more effective therapies.

Polyfunctional, Proinflammatory, Tissue‐Resident Memory Phenotype and Function of Synovial Interleukin‐17A+CD8+ T Cells in Psoriatic Arthritis

“…However, Tc17 cells lacked significant expression of other cytolytic machinery (perforin and LAMP-1). Most studies to date in both mice and humans have shown that Tc17 cells lack cytolytic function (29,31,46,47), although some evidence for cytotoxic function has been reported (24,48). An interesting alternative interpretation of our data is that the secretion of granzymes is not cytolytic but leads to extracellular matrix degradation or promotion of inflammation (49,50).…”

“…A possible explanation for these findings is that synovial Tc17 and Tc1 cells may have shared ancestry, which raises the question of plasticity between these subsets. Adoptive transfer of in vitro generated Tc17 cells into recipient mice showed that Tc17 cells can switch to an IL‐17A–negative Tc1 profile . A direct demonstration of this phenomenon came from an elegant IL‐17A fate‐mapping study using reporter donor IL‐17 Cre Rosa26 eYFP .…”

Normal human enthesis harbours conventional CD4+ and CD8+ T cells with regulatory features and inducible IL-17A and TNF expression

“…30 Tc17 cells are highly plastic in nature and can switch to interferon-γ producing Tc1 cells in certain tissues. 31 Entheseal CD4+ and CD8+ T cells are transcriptionally, phenotypically and functionally distinct from matched recirculating peripheral T cells. Entheseal T cells also have higher expression of transcripts involved in repair and tissue homeostasis, such as IL-10, TGFβ1 and VEGF-A when compared with their blood counterparts.…”

Animal Models of Cryptococcus neoformans in Identifying Immune Parameters Associated With Primary Infection and Reactivation of Latent Infection

“…T cells can be divided into CD4 + and CD8 + subsets, each possessing protective capabilities in the absence of the other during infection with C. neoformans (251)(252)(253)(254)(255). T cell-mediated immunity represents the most widely accepted potent host defense against C. neoformans infections, as well as the deepest downfall when a host is lymphopenic such as in HIV/AIDS patients.…”