Biochemical signaling of PD-1 on T cells and its functional implications

Cancer Journal (United States)

Volumn 20, Issue 4, 2014, Pages 265-271

  Boussiotis, Vassiliki A ^a   Chatterjee, Pranam ^a   Li, Lequn ^a  

^a BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

Author keywords

Controlling autoimmunity; PD 1; peripheral tolerance; T cell anergy

Indexed keywords

CD28 ANTIGEN; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; ICOS PROTEIN; INTERLEUKIN 2; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROGRAMMED CELL DEATH 1; PROTEIN; SIALIC ACID BINDING IMMUNOGLOBULIN LIKE LECTIN; TRANSFORMING GROWTH FACTOR BETA; TYROSINE; UNCLASSIFIED DRUG; PDCD1LG2 PROTEIN, HUMAN; PROGRAMMED DEATH 1 LIGAND 1; PROGRAMMED DEATH 1 LIGAND 2; PROGRAMMED DEATH 1 RECEPTOR;

CARBOXY TERMINAL SEQUENCE; CELL CYCLE; CELL CYCLE PROGRESSION; CELL DEATH; CELL LINE; DEPHOSPHORYLATION; EFFECTOR CELL; ENZYME ACTIVITY; GENE EXPRESSION; HUMAN; IMMUNORECEPTOR TYROSINE BASED INHIBITION MOTIF; LIGATION; MASS SPECTROMETRY; NONHUMAN; NUCLEAR REPROGRAMMING; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN STRUCTURE; REGULATORY T LYMPHOCYTE; REVIEW; SIGNAL TRANSDUCTION; SITE DIRECTED MUTAGENESIS; STABLE EXPRESSION; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION; ANIMAL; AUTOIMMUNITY; IMMUNOLOGICAL TOLERANCE; IMMUNOLOGY;

ANIMALS; ANTIGENS, CD274; AUTOIMMUNITY; HUMANS; IMMUNE TOLERANCE; PROGRAMMED CELL DEATH 1 LIGAND 2 PROTEIN; PROGRAMMED CELL DEATH 1 RECEPTOR; SIGNAL TRANSDUCTION; T-LYMPHOCYTES;

EID: 84905966344     PISSN: 15289117     EISSN: 1540336X     Source Type: Journal    
DOI: 10.1097/PPO.0000000000000059     Document Type: Review

References (81)

1. Terawaki S, Chikuma S, Shibayama S, et al. IFN-alpha directly promotes programmed cell death-1 transcription and limits the duration of T cell-mediated immunity. J Immunol. 2011;186:2772-2779.
2. Kinter AL, Godbout EJ, McNally JP, et al. The common gamma-chain cytokines IL-2, IL-7, IL-15, and IL-21 induce the expression of programmed death-1 and its ligands. J Immunol. 2008;181:6738-6746.
3. Chemnitz JM, Parry RV, Nichols KE, et al. SHP-1 and SHP-2 associate with immunoreceptor tyrosine-based switch motif of programmed death 1 upon primary human T cell stimulation, but only receptor ligation prevents T cell activation. J Immunol. 2004;173:945-954. (Pubitemid 38924267)
4. Agata Y, Kawasaki A, Nishimura H, et al. Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes. Int Immunol. 1996;8:765-772. (Pubitemid 26148299)
5. Ishida Y, Agata Y, Shibahara K, et al. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J. 1992;11:3887-3895.
6. Nishimura H, Agata Y, Kawasaki A, et al. Developmentally regulated expression of the PD-1 protein on the surface of double-negative (CD4 ?CD8?) thymocytes. Int Immunol. 1996;8:773-780. (Pubitemid 26148300)
7. Moll M, Kuylenstierna C, Gonzalez VD, et al. Severe functional impairment and elevated PD-1 expression in CD1d-restricted NKT cells retained during chronic HIV-1 infection. Eur J Immunol. 2009;39:902-911.
8. Yamazaki T, Akiba H, Iwai H, et al. Expression of programmed death 1 ligands by murine T cells and APC. J Immunol. 2002;169:5538-5545. (Pubitemid 35291652)
9. Okazaki T, Maeda A, Nishimura H, et al. PD-1 immunoreceptor inhibits B cell receptor-mediated signaling by recruiting src homology 2-domaincontaining tyrosine phosphatase 2 to phosphotyrosine. Proc Natl Acad Sci USA. 2001;98:13866-13871. (Pubitemid 33115990)
10. Tseng SY, OtsujiM, Gorski K, et al. B7-DC, a new dendritic cell molecule with potent costimulatory properties for T cells.JExpMed. 2001;193:839-846.
11. Latchman Y, Wood CR, Chernova T, et al. PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat Immunol. 2001;2:261-268. (Pubitemid 33706004)
12. Dong H, Zhu G, Tamada K, et al. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med. 1999;5:1365-1369.
13. Keir ME, Liang SC, Guleria I, et al. Tissue expression of PD-L1 mediates peripheral T cell tolerance. J Exp Med. 2006;203:883-895.
14. Brown JA, Dorfman DM, Ma FR, et al. Blockade of programmed death-1 ligands on dendritic cells enhances T cell activation and cytokine production. J Immunol. 2003;170:1257-1266. (Pubitemid 36139491)
15. KeirME, ButteMJ, FreemanGJ, et al. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol. 2008;26:677-704. (Pubitemid 351600389)
16. Butte MJ, Keir ME, Phamduy TB, et al. Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses. Immunity. 2007;27:111-122. (Pubitemid 47089023)
17. Keir ME, Freeman GJ, Sharpe AH. PD-1 regulates self-reactive CD8+ T cell responses to antigen in lymph nodes and tissues. J Immunol. 2007;179:5064-5070.
18. Probst HC, McCoy K, Okazaki T, et al. Resting dendritic cells induce peripheral CD8+ T cell tolerance through PD-1 and CTLA-4. Nat Immunol. 2005;6:280-286. (Pubitemid 41724765)
19. Reynoso ED, Elpek KG, Francisco L, et al. Intestinal tolerance is converted to autoimmune enteritis upon PD-1 ligand blockade. J Immunol. 2009;182:2102-2112.
20. Patsoukis N, Sari D, Boussiotis VA. PD-1 inhibits T cell proliferation by upregulating p27 and p15 and suppressing Cdc25A. Cell Cycle. 2012;11:4305-4309.
21. Okazaki T, Okazaki IM, Wang J, et al. PD-1 and LAG-3 inhibitory coreceptors act synergistically to prevent autoimmunity in mice. J Exp Med. 2011;208:395-407.
22. Oestreich KJ, Yoon H, Ahmed R, et al. NFATc1 regulates PD-1 expression upon T cell activation. J Immunol. 2008;181:4832-4839.
23. Francisco LM, Salinas VH, Brown KE, et al. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J ExpMed. 2009;206:3015-3029.
24. Nishimura H, Nose M, Hiai H, et al. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motifcarrying immunoreceptor. Immunity. 1999;11:141-151. (Pubitemid 29428807)
25. Nishimura H, Okazaki T, TanakaY, et al. Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science. 2001;291:319-322. (Pubitemid 32096320)
26. Okazaki T, Otaka Y, Wang J, et al. Hydronephrosis associated with antiurothelial and antinuclear autoantibodies in BALB/c-Fcgr2b?/?Pdcd1 ?/? mice. J Exp Med. 2005;202:1643-1648. (Pubitemid 41815870)
27. Yoshida T, Jiang F, Honjo T, et al. PD-1 deficiency reveals various tissuespecific autoimmunity by H-2b and dose-dependent requirement of H-2g7 for diabetes in NOD mice. Proc Natl Acad Sci USA. 2008;105:3533-3538. (Pubitemid 351723587)
28. Wang J, Yoshida T, Nakaki F, et al. Establishment of NOD-Pdcd1?/? mice as an efficient animal model of type I diabetes. Proc Natl Acad Sci USA. 2005;102:11823-11828. (Pubitemid 41170809)
29. Nielsen C, Hansen D, Husby S, et al. Association of a putative regulatory polymorphism in the PD-1 gene with susceptibility to type 1 diabetes. Tissue Antigens. 2003;62:492-497. (Pubitemid 37479307)
30. Prokunina L, Castillejo-Lopez C, Oberg F, et al. A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans. Nat Genet. 2002;32:666-669. (Pubitemid 35435182)
31. Currie AJ, Prosser A, McDonnell A, et al. Dual control of antitumor CD8 T cells through the programmed death-1/programmed death-ligand 1 pathway and immunosuppressive CD4 T cells: regulation and counterregulation. J Immunol. 2009;183:7898-7908.
32. Kuang DM, Zhao Q, Peng C, et al. Activated monocytes in peritumoral stroma of hepatocellular carcinoma foster immune privilege and disease progression through PD-L1. J Exp Med. 2009;206:1327-1337.
33. Zhang L, Gajewski TF, Kline J. PD-1/PD-L1 interactions inhibit antitumor immune responses in a murine acute myeloid leukemia model. Blood. 2009;114:1545-1552.
34. Watanabe T, Bertoletti A, Tanoto TA. PD-1/PD-L1 pathway and T-cell exhaustion in chronic hepatitis virus infection.J ViralHepat. 2010;17:453-458.
35. Day CL, Kaufmann DE, Kiepiela P, et al. PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature. 2006;443:350-354. (Pubitemid 44435155)
36. Riley JL. PD-1 signaling in primary T cells. Immunol Rev. 2009;229:114-125.
37. Neel BG, Gu H, Pao L. The 'Shp'ing news: SH2 domain-containing tyrosine phosphatases in cell signaling. Trends Biochem Sci. 2003;28:284-293. (Pubitemid 36776291)
38. Shlapatska LM, Mikhalap SV, Berdova AG, et al. CD150 association with either the SH2-containing inositol phosphatase or the SH2-containing protein tyrosine phosphatase is regulated by the adaptor protein SH2D1A. J Immunol. 2001;166:5480-5487. (Pubitemid 32374169)
39. Crocker PR, Paulson JC, Varki A. Siglecs and their roles in the immune system. Nat Rev Immunol. 2007;7:255-266. (Pubitemid 46480955)
40. Riley JL, JuneCH. The road to recovery: translating PD-1 biology into clinical benefit. Trends Immunol. 2007;28:48-50. (Pubitemid 46176731)
41. Okazaki T, Honjo T. The PD-1-PD-L pathway in immunological tolerance. Trends Immunol. 2006;27:195-201.
42. Parry RV, Chemnitz JM, Frauwirth KA, et al. CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms. Mol Cell Biol. 2005;25:9543-9553. (Pubitemid 41507854)
43. Sheppard KA, Fitz LJ, Lee JM, et al. PD-1 inhibits T-cell receptor induced phosphorylation of the ZAP70/CD3ζ signalosome and downstream signaling to PKCθ. FEBS Lett. 2004;574:37-41. (Pubitemid 39200891)
44. Yokosuka T, Takamatsu M, Kobayashi-ImanishiW, et al. Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2. J Exp Med. 2012;209:1201-1217.
45. Chatterjee P, Patsoukis N, Freeman GJ, et al. Distinct roles of PD-1 ITSM and ITIM in regulating interaction of PD-1 with SHP-2, ZAP-70 and Lck, and PD-1-mediated inhibitory function. Presented at the Annual Meeting of the American Society of Hematology, 2013. Abstract 191.
46. Waterhouse P, Penninger JM, Timms E, et al. Lymphoproliferative disorders with early lethality in mice deficient in CTLA-4. Science. 1995;270: 985-988.
47. Chuang E, Fisher TS, Morgan RW, et al. The CD28 and CTLA-4 receptors associate with the serine/threonine phosphatase PP2A. Immunity. 2000;13: 313-322.
48. Patsoukis N, Li L, Sari D, et al. PD-1 increases PTEN phosphatase activity while decreasing PTEN protein stability by inhibiting casein kinase 2. Mol Cell Biol. 2013;33:3091-3098.
49. Vazquez F, Ramaswamy S, Nakamura N, et al. Phosphorylation of the PTEN tail regulates protein stability and function. Mol Cell Biol. 2000;20:5010-5018. (Pubitemid 30431555)
50. Torres J, Pulido R. The tumor suppressor PTEN is phosphorylated by the protein kinase CK2 at its C terminus. Implications for PTEN stability to proteasome-mediated degradation. J Biol Chem. 2001;276:993-998. (Pubitemid 32096519)
51. LitchfieldDW. Protein kinase CK2: structure, regulation and role in cellular decisions of life and death. Biochem J. 2003;369:1-15. (Pubitemid 36174119)
52. Patsoukis N, Brown J, Petkova V, et al. Selective effects of PD-1 on Akt and Ras pathways regulate molecular components of the cell cycle and inhibit T cell proliferation. Sci Signal. 2012;5:ra46.
53. Roose JP, Mollenauer M, Gupta VA, et al. A diacylglycerol-protein kinase C-RasGRP1 pathway directs Ras activation upon antigen receptor stimulation of T cells. Mol Cell Biol. 2005;25:4426-4441. (Pubitemid 40705750)
54. Ebinu JO, Stang SL, Teixeira C, et al. RasGRP links T-cell receptor signaling to Ras. Blood. 2000;95:3199-3203. (Pubitemid 30321173)
55. Ebinu JO, Bottorff DA, Chan EY, et al. RasGRP, a Ras guanyl nucleotide-releasing protein with calcium-and diacylglycerol-bindingmotifs. Science. 1998;280:1082-1086. (Pubitemid 28234950)
56. Bivona TG, Perez De Castro I, Ahearn IM, et al. Phospholipase Cgamma activates Ras on the Golgi apparatus by means of RasGRP1. Nature. 2003;424:694-698. (Pubitemid 36987996)
57. Appleman LJ, van Puijenbroek AA, Shu KM, et al. CD28 costimulation mediates down-regulation of p27kip1 and cell cycle progression by activation of the PI3K/PKB signaling pathway in primary human T cells. J Immunol. 2002;168:2729-2736. (Pubitemid 34211650)
58. Appleman LJ, Berezovskaya A, Grass I, et al. CD28 costimulationmediates T cell expansion via IL-2-independent and IL-2-dependent regulation of cell cycle progression. J Immunol. 2000;164:144-151. (Pubitemid 30012984)
59. Boonen GJ, vanDijk AM, Verdonck LF, et al. CD28 induces cell cycle progression by IL-2-independent down-regulation of p27kip1 expression in human peripheral T lymphocytes. Eur J Immunol. 1999;29:789-798. (Pubitemid 29119058)
60. Carrano AC, Eytan E, Hershko A, et al. SPK2 is required for ubiquitinmediated degradation of the cdk inhibitor p27.Nat Cell Biol. 1999;1:193-199. (Pubitemid 129500937)
61. Appleman LJ, Chernova I, Li L, et al. CD28 costimulation mediates transcription of SKP2 and CKS1, the substrate recognition components of SCFSkp2 ubiquitin ligase that leads p27kip1 to degradation. Cell Cycle. 2006;5:2123-2129. (Pubitemid 44553747)
62. Matsuura I, Denissova NG, Wang G, et al. Cyclin-dependent kinases regulate the antiproliferative function of Smads. Nature. 2004;430:226-231. (Pubitemid 38902433)
63. Boutros R, Dozier C, Ducommun B. The when and wheres of CDC25 phosphatases. Curr Opin Cell Biol. 2006;18:185-191. (Pubitemid 43375887)
64. Sherr CJ, Roberts JM. Living with or without cyclins and cyclin-dependent kinases. Genes Dev. 2004;18:2699-2711. (Pubitemid 39507762)
65. Harbour JW, Luo RX, Dei Santi A, et al. Cdk phosphorylation triggers sequential intramolecular interactions that progressively block Rb functions as cells move through G1. Cell. 1999;98:859-869. (Pubitemid 29446902)
66. Harbour JW, Dean DC. Chromatin remodeling and Rb activity. Curr Opin Cell Biol. 2000;12:685-689.
67. Hua XH, Newport J. Identification of a preinitiation step in DNA replication that is independent of origin recognition complex and cdc6, but dependent on cdk2. J Cell Biol. 1998;140:271-281. (Pubitemid 28078391)
68. Harbour JW, Dean DC. The Rb/E2F pathway: expanding roles and emerging paradigms. Genes Dev. 2000;14:2393-2409.
69. Wells AD. Cyclin-dependent kinases: molecular switches controlling anergy and potential therapeutic targets for tolerance. Semin Immunol. 2007; 19:173-179. (Pubitemid 46824072)
70. Wohler J, Bullard D, Schoeb T, et al. LFA-1 is critical for regulatory T cell homeostasis and function. Mol Immunol. 2009;46:2424-2428.
71. MarskiM, Kandula S, Turner JR, et al. CD18 is required for optimal development and function of CD4+CD25+ T regulatory cells. J Immunol. 2005;175:7889-7897. (Pubitemid 41798349)
72. Reedquist KA, Ross E, Koop EA, et al. The small GTPase, Rap1, mediates CD31-induced integrin adhesion. J Cell Biol. 2000;148:1151-1158.
73. Li L, Kim J, Boussiotis VA. Rap1A regulates generation of T regulatory cells via LFA-1-dependent and LFA-1-independent mechanisms. Cell Immunol. 2010;266:7-13.
74. Frauwirth KA, Thompson CB. Regulation of T lymphocyte metabolism. J Immunol. 2004;172:4661-4665. (Pubitemid 38456383)
75. Rathmell JC, Vander Heiden MG, Harris MH, et al. In the absence of extrinsic signals, nutrient utilization by lymphocytes is insufficient to maintain either cell size or viability. Mol Cell. 2000;6:683-692.
76. Frauwirth KA, Riley JL, Harris MH, et al. The CD28 signaling pathway regulates glucose metabolism. Immunity. 2002;16:769-777. (Pubitemid 34786476)
77. Wieman HL, Wofford JA, Rathmell JC. Cytokine stimulation promotes glucose uptake via phosphatidylinositol-3 kinase/Akt regulation of Glut1 activity and trafficking.Mol Biol Cell. 2007;18:1437-1446. (Pubitemid 46626638)
78. Chang CH, Curtis JD, Maggi LB Jr, et al. Posttranscriptional control of T cell effector function by aerobic glycolysis. Cell. 2013;153: 1239-1251.
79. Pearce EL, Walsh MC, Cejas PJ, et al. Enhancing CD8 T-cell memory by modulating fatty acid metabolism. Nature. 2009;460:103-107.
80. Michalek RD, Gerriets VA, Jacobs SR, et al. Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets. J Immunol. 2011;186:3299-3303.
81. Patsoukis N, Chatterjee P, Sari D, et al. PD-1 induces metabolic reprogramming of activated ""T cells from glycolysis to lipid oxidation. Presented at the Annual Meeting of the American Society of Hematology, 2013. Abstract #187.