Abstract The research on the immunoregulatory effect of programmed death-1 (PD-1) in infectious diseases mainly focuses on chronic viral infection, but there are few studies on acute viral infection. In chronic viral infection, PD-1 is highly expressed on the surface of CD8+ T cells, which is a sign of CD8+ T cell depletion. Recent studies have shown that in chronic viral infection, PD-1 is also highly expressed on the surface of regulatory T cells and binds to programmed death-ligand 1 (PD-L1) on the surface of exhausted CD8+ T cells, resulting in a stronger inhibitory effect on CD8+ T cell immunity. Blocking the PD-1/PD-L1 signaling pathway between exhausted CD8+ T cells and regulatory T cells can significantly reverse the depletion of CD8+ T cells and greatly improve the antiviral effect of CD8+ T cells. However, the role of the PD-1/PD-L1 signaling pathway in acute viral infection remains unknown. This article summarizes the latest research on PD-1 in infectious diseases and discusses its role in acute and chronic viral infection.
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[J]. EMBO J, 1992, 11(11):3887-3895.
[2]
Legat A, Speiser DE, Pircher H, et al. Inhibitory receptor expression depends more dominantly on differentiation and activation than "exhaustion" of human CD8 T cells[J]. Front Immunol, 2013, 4:455.
[3]
Bardhan K, Anagnostou T, Boussiotis VA. The PD1:PD-L1/2 pathway from discovery to clinical implementation[J]. Front Immunol, 2016, 7:550.
[4]
Roemer MG, Advani RH, Ligon AH, et al. PD-L1 and PD-L2 genetic alterations define classical hodgkin lymphoma and predict outcome[J]. J Clin Oncol, 2016, 34(23):2690-2697.
[5]
Keir ME, Butte MJ, Freeman GJ, et al. PD-1 and its ligands in tolerance and immunity[J]. Annu Rev Immunol, 2008, 26:677-704.
[6]
Okazaki T, Honjo T. PD-1 and PD-1 ligands:from discovery to clinical application[J]. Int Immunol, 2007, 19(7):813-824.
[7]
Drabczyk-Pluta M, Werner T, Hoffmann D, et al. Granulocytic myeloid-derived suppressor cells suppress virus-specific CD8+ T cell responses during acute friend retrovirus infection[J]. Retrovirology, 2017, 14(1):42.
[8]
Speiser DE, Utzschneider DT, Oberle SG, et al. T cell differentiation in chronic infection and cancer:functional adaptation or exhaustion?[J]. Nat Rev Immunol, 2014, 14(11):768-774.
[9]
Wykes MN, Lewin SR. Immune checkpoint blockade in infectious diseases[J]. Nat Rev Immunol, 2017.[Epub ahead of print]
[10]
Jin HT, Jeong YH, Park HJ, et al. Mechanism of T cell exhaustion in a chronic environment[J]. BMB Rep, 2011, 44(4):217-231.
[11]
See JX, Chandramathi S, Abdulla MA, et al. Persistent infection due to a small-colony variant of Burkholderia pseudomallei leads to PD-1 upregulation on circulating immune cells and mononuclear infiltration in viscera of experimental BALB/c mice[J]. PLoS Negl Trop Dis, 2017, 11(8):e0005702.
[12]
Barber DL, Wherry EJ, Masopust D, et al. Restoring function in exhausted CD8 T cells during chronic viral infection[J]. Nature, 2006, 439(7077):682-687.
[13]
Liu Z, Li S, Liu Y, et al. PD1 is highly expressed in diffuse large B-cell lymphoma with hepatitis B virus infection[J]. PLoS One, 2017, 12(6):e0180390.
[14]
Zhang G, Li N, Zhang P, et al. PD-1 mRNA expression is associated with clinical and viral profile and PD13'-untranslated region polymorphism in patients with chronic HBV infection[J]. Immunol Lett, 2014, 162(1 Pt A):212-216.
[15]
Barrett L, Trehanpati N, Poonia S, et al. Hepatic compartmentalization of exhausted and regulatory cells in HIV/HCV-coinfected patients[J]. J Viral Hepat, 2015, 22(3):281-288.
[16]
Zhang JY, Zhang Z, Wang X, et al. PD-1 up-regulation is correlated with HIV-specific memory CD8+ T-cell exhaustion in typical progressors but not in long-term nonprogressors[J]. Blood, 2007, 109(11):4671-4678.
[17]
Larsson M, Shankar EM, Che KF, et al. Molecular signatures of T-cell inhibition in HIV-1 infection[J]. Retrovirology, 2013, 10:31.
[18]
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[J]. Nature, 2006, 443(7109):350-354.
[19]
Virgin HW, Wherry EJ, Ahmed R. Redefining chronic viral infection[J]. Cell, 2009, 138(1):30-50.
[20]
Sen DR, Kaminski J, Barnitz RA, et al. The epigenetic landscape of T cell exhaustion[J]. Science, 2016, 354(6316):1165-1169.
[21]
Wherry EJ. T cell exhaustion[J]. Nat Immunol, 2011, 12(6):492-499.
[22]
Ren J, Liu X, Fang C, et al. Multiplex genome editing to generate universal CAR T cells resistant to PD1 inhibition[J]. Clin Cancer Res, 2017, 23(9):2255-2266.
[23]
Arasanz H, Gato-Cañas M, Zuazo M, et al. PD1 signal transduction pathways in T cells[J]. Oncotarget, 2017, 8(31):51936-51945.
[24]
Motzer RJ, Escudier B, McDermott DF, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma[J]. N Engl J Med, 2015, 373(19):1803-1813.
[25]
Fuller MJ, Callendret B, Zhu B, et al. Immunotherapy of chronic hepatitis C virus infection with antibodies against programmed cell death-1(PD-1)[J]. Proc Natl Acad Sci U S A, 2013, 110(37):15001-15006.
[26]
Tang L, Bai J, Chung CS, et al. Programmed cell death receptor ligand 1 modulates the regulatory T cells' capacity to repress shock/sepsis-induced indirect acute lung injury by recruiting phosphatase SRC homology region 2 domain-containing phosphatase 1[J]. Shock, 2015, 43(1):47-54.
[27]
Punkosdy GA, Blain M, Glass DD, et al. Regulatory T-cell expansion during chronic viral infection is dependent on endogenous retroviral superantigens[J]. Proc Natl Acad Sci U S A, 2011, 108(9):3677-3682.
[28]
Bruneau J, Canioni D, Renand A, et al. Regulatory T-cell depletion in angioimmunoblastic T-cell lymphoma[J]. Am J Pathol, 2010, 177(2):570-574.
[29]
Cochain C, Chaudhari SM, Koch M, et al. Programmed cell death-1 deficiency exacerbates T cell activation and atherogenesis despite expansion of regulatory T cells in atherosclerosis-prone mice[J]. PLoS One, 2014, 9(4):e93280.
[30]
Tripathi S, Guleria I. Role of PD1/PDL1 pathway, and TH17 and treg cells in maternal tolerance to the fetus[J]. Biomed J, 2015, 38(1):25-31.
[31]
Chowdhury A, Del Rio Estrada PM, Tharp GK, et al. Decreased T follicular regulatory cell/T follicular helper cell (TFH) in simian immunodeficiency virus-infected rhesus macaques may contribute to accumulation of TFH in chronic infection[J]. J Immunol, 2015, 195(7):3237-3247.
[32]
Park HJ, Park JS, Jeong YH, et al. PD-1 upregulated on regulatory T cells during chronic virus infection enhances the suppression of CD8+ T cell immune response via the interaction with PD-L1 expressed on CD8+ T cells[J]. J Immunol, 2015, 194(12):5801-5811.
[33]
Penaloza-MacMaster P, Kamphorst AO, Wieland A, et al. Interplay between regulatory T cells and PD-1 in modulating T cell exhaustion and viral control during chronic LCMV infection[J]. J Exp Med, 2014, 211(9):1905-1918.
[34]
Akhmetzyanova I, Drabczyk M, Neff CP, et al. PD-L1 expression on retrovirus-infected cells mediates immune escape from CD8+ T cell killing[J]. PLoS Pathog, 2015, 11(10):e1005224.
[35]
Park HJ, Kusnadi A, Lee EJ, et al. Tumor-infiltrating regulatory T cells delineated by upregulation of PD-1 and inhibitory receptors[J]. Cell Immunol, 2012, 278(1-2):76-83.
[36]
Dyck L, Wilk MM, Raverdeau M, et al. Anti-PD-1 inhibits Foxp3+ Treg cell conversion and unleashes intratumoural effector T cells thereby enhancing the efficacy of a cancer vaccine in a mouse model[J]. Cancer Immunol Immunother, 2016, 65(12):1491-1498.
[37]
Rao M, Valentini D, Dodoo E, et al. Anti-PD-1/PD-L1 therapy for infectious diseases:learning from the cancer paradigm[J]. Int J Infect Dis, 2017, 56:221-228.
[38]
Dyck L, Mills KHG. Immune checkpoints and their inhibition in cancer and infectious diseases[J]. Eur J Immunol, 2017, 47(5):765-779.
[39]
Pauken KE, Sammons MA, Odorizzi PM, et al. Epigenetic stability of exhausted T cells limits durability of reinvigoration by PD-1 blockade[J]. Science, 2016, 354(6316):1160-1165.
[40]
Liu Q, Li CS. Programmed cell death-1/programmed death-ligand 1 pathway:a new target for sepsis[J]. Chin Med J (Engl), 2017, 130(8):986-992.
[41]
Lafon M, Mégret F, Meuth SG, et al. Detrimental contribution of the immuno-inhibitor B7-H1 to rabies virus encephalitis[J]. J Immunol, 2008, 180(11):7506-7515.
[42]
Yue F, Zhu YP, Zhang YF, et al. Up-regulated expression of PD-1 and its ligands during acute classical swine fever virus infection in swine[J]. Res Vet Sci, 2014, 97(2):251-256.
[43]
Rutigliano JA, Sharma S, Morris MY, et al. Highly pathological influenza A virus infection is associated with augmented expression of PD-1 by functionally compromised virus-specific CD8+ T cells[J]. J Virol, 2014, 88(3):1636-1651.
[44]
Zelinskyy G, Myers L, Dietze KK, et al. Virus-specific CD8+ T cells upregulate programmed death-1 expression during acute friend retrovirus infection but are highly cytotoxic and control virus replication[J]. J Immunol, 2011, 187(7):3730-3737.
[45]
Erickson JJ, Gilchuk P, Hastings AK, et al. Viral acute lower respiratory infections impair CD8+ T cells through PD-1[J]. J Clin Invest, 2012, 122(8):2967-2982.
[46]
Odorizzi PM, Pauken KE, Paley MA, et al. Genetic absence of PD-1 promotes accumulation of terminally differentiated exhausted CD8+ T cells[J]. J Exp Med, 2015, 212(7):1125-1137.
[47]
Prasad S, Hu S, Sheng WS, et al. The PD-1:PD-L1 pathway promotes development of brain-resident memory T cells following acute viral encephalitis[J]. J Neuroinflammation, 2017, 14(1):82.
[48]
Duraiswamy J, Ibegbu CC, Masopust D, et al. Phenotype, function, and gene expression profiles of programmed death-1(hi) CD8 T cells in healthy human adults[J]. J Immunol, 2011, 186(7):4200-4212.
[49]
Hong JJ, Amancha PK, Rogers K, et al. Re-evaluation of PD-1 expression by T cells as a marker for immune exhaustion during SIV infection[J]. PLoS One, 2013, 8(3):e60186.
[50]
Le Burel S, Champiat S, Routier E, et al. Onset of connective tissue disease following anti-PD1/PD-L1 cancer immunotherapy[J]. Ann Rheum Dis, 2017.[Epub ahead of print]
[51]
Sharpe AH, Pauken KE. The diverse functions of the PD1 inhibitory pathway[J]. Nat Rev Immunol, 2017.[Epub ahead of print].
