Table 1.
Immune checkpoints expression and functions/properties.
| Immune Checkpoints |
Expression and Functions/Properties | References |
|---|---|---|
| OX40 (CD134) | Mainly expressed on activated APCs | [34] |
| Expressed on hematopoietic cells such as activated NK cells, NKT cells, mast cells or the responding CD4+ T cells, and non-hematopoietic cells, such as endothelial cells or smooth muscle cells | [35,36] | |
| An increase in the survival of T cells and their transition to memory T cells during the immune response | [37] | |
| GITR | Inhibition of suppressive activity of Tregs and prolongation of T-effector-cell survival |
[45,46] |
| Present on the membrane of NK cells and, to a lesser extent, B lymphocytes, macrophages and DCs | [47] | |
| Increases survival, activation, and stimulation of T-cell proliferation by increasing TCR-induced proliferation, cytokine production, and blocking anti-CD3-induced T-cell apoptosis | [48,49] | |
| Differentiation of naive CD4+ T cells into Th17 cells | [50] | |
| Activation of the p38 MAP signaling pathway and the STAT3 signaling pathway influencing the development of Th17 cells | [51] | |
| ICOS | Expressed on activated CD4+ and CD8+ T cells, presumably regulates adaptive T-cell response | [52,53] |
| Expressed on Th1, Th2, Th17, Tfh, Tfr, Treg, Tr1, and innate lymphoid cells | [54,55] | |
| Participation in differentiation, proliferation, and survival of Tregs | [56,57,58] | |
| Regulation of the humoral immune response, namely in the formation of germinal centers and the generation of Ig class switching | [55] | |
| PD-1/PDL1 | PD-1 is expressed on activated T cells, B cells, and monocytes | [59] |
| PD-L1 expression on proliferation and activation of T cells by interacting with PD-1. | [60] | |
| PD-1 negatively regulates the TCR signal by recruiting SHP-2 to the phosphorylated tyrosine residue in the cytoplasmic region | [61] | |
| CTLA-4 | Inhibition of T-cell proliferation, cell cycle progression, IL-2 production, and differentiation of T cells | [62] |
| CD40/CD40L | CD-40 is expressed mainly on B cells and regulation of B-cell proliferation | [63] |
| CD40L expressed mainly on T cells | [64] | |
| T-cell-dependent B-cell differentiation and activation | [65] |
Abbreviations: APCs, antigen-presenting cells; NK cells, natural killer cells; NKT cells, natural killer T cells; Tregs, T regulatory cells; DCs, dendritic cells; TCR, T-cell receptor; Th, T helper; MAP, Mitogen-activated protein kinase; STAT3, Signal transducer and activator of transcription 3; Tfh, T follicular helper cells; Tfr, T follicular regulatory cells; Tr1, type 1 regulatory T cells; SHP-2, src homology two-domain-containing tyrosine phosphatase 2.