Table 5.

Positive signals of T-cell effector activity through differentiation.

Signal/Receptor	Producer/Target	Mechanisms	Therapy
IL7/IL7R+IL2RG	Fibroblastic reticular cell/CD8 T cell	IL-7 generated the stem-cell memory T cells from naive CD8 T cells (150).
IL12A,B/IL12R IFN-α/β/IFNAR1, 2	Phagocytic cells, B cells, DC/CD8 T cells	IL12 and IFN-α/β provide a third signal, along with Antigen and costimulation, to support CD8 T memory programming, which involves chromatin remodeling and regulation of genes such as TBX21 (T-bet) and EOMES (190, 191). IL12 also polarizes naive T cells into Th1 cells (192).
IL15/IL15RA, IL2RB, IL2RG	Monocytes, macrophages, DC/CD8+ T cells	IL15 induces the generation of antigen-specific memory T cells (193).
IL21/IL21R+IL2RG	Th2, NKT cells/CD8 T cell	IL21 suppresses the antigen-induced CD8+ T-cell differentiation from naive T cells to effector T cells and induced stem-like properties, which allows CD8+ T cells for secondary expansion after adoptive transfer (194).
CD40L/CD40	DC, macrophages, B cells, T cells, mast cells/CD40+ T cell	CD40L/CD40 increases T-cell proliferation, CD8+ T-cell immunity, and memory (195).
TGFB+IL6+IL23	In-vitro culture treatment.	CD4+ T-cell differentiates into Th17 via TGFB and IL6 (196). IL23 maintains the proliferation of Th17. (Fn. 10) Th17 are long-lived cells with stem-like properties. It can also convert into a Th1-lineage over time, switching from IL17 secreting cells to IFNγ producers or IFNγ/IL17A double producers (197).	Transfer of Th17 cells enhances survival and tumor regression better than Th1 cells in a murine melanoma model (198).
CCL21/CCR7, CXCR3	Lymphatic vessels, stroma cells, HEV in lymph nodes/CD4 T cells (35, 36)	CCL21 promotes Th1 polarization (141).