Table 1.

Summary of Mouse and Human Virtual Memory CD8 T Cell Subsets Main Characteristics

Name	Species	Membrane markers	Transcription factor signature	TCR repertoire	Response to TCR stimulation	Innate-like functions	Central/peripheral differentiation	Homeostasis throughout life	Pathological context
TVM	Mouse	CD8, CD44hi, CD122hi, CD49dlo, IL-4R, IFN-I R	Eomeshi	Diverse, but nonsimilar to TN repertoire	Yes, with low proliferation	Highly responsive to IL-15 IFNγ secretion in response to IL-12/IL-18	IL-15 and Eomes dependent, mainly in periphery Precursors in the thymus	Increase with age	Bacterial and viral infections Tumor infiltration in several cancer models
TIM/TVM	Human	CD8, KIR+ and/or NKG2A+, CD62L, CD122, CD45RA+, CCR7− CD27− as defined in Jacomet et al., 2015	Eomes+, T-bet+	Unknown	Yes	IFNγ secretion in response to IL-12/IL-18 CD107a degranulation induced by anti-CD16 or MHC class I- target cells Highly responsive to IL-15	Unknown, but present in cord blood, fetal thymus, and spleen	Not consensual	High antitumoral potential (CML, ovarian. and breast cancers) Expanded in HIV patients
TIM/TVM NKG2A+	Human	CD8, NKG2A+, CD45RA+, TIGIT−, CD226+ as defined in Pieren et al., 2021	Eomesint	Unknown	Yes, proliferation similar to other CD8 T cells	High IFNγ secretion in response to IL-12/IL-18	Unknown	Decline with age	High antitumoral potential, synergy with NK cells (NKG2A as a checkpoint inhibitor)
TIM/TVM KIR+	Human	CD8, KIR+, CD45RA+, TIGIT+, CD226− as defined in Pieren et al., 2021	Eomeshi, Helios	Less diverse than other CD8 T cells	Yes, proliferation lower than other CD8 T cells	Low IFNγ secretion in response to IL-12/IL-18	Unknown	Increase with age	Putative CD8 Treg suppressive activity in autoimmune and infectious diseases