程序性死亡因子1在病毒感染性疾病中的作用

陆富策, 农光民

中国当代儿科杂志 ›› 2018, Vol. 20 ›› Issue (1) : 77-82.

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中国当代儿科杂志 ›› 2018, Vol. 20 ›› Issue (1) : 77-82. DOI: 10.7499/j.issn.1008-8830.2018.01.016
综述

程序性死亡因子1在病毒感染性疾病中的作用

  • 陆富策, 农光民
作者信息 +

Role of programmed death-1 in viral infectious diseases

  • LU Fu-Ce, NONG Guang-Min
Author information +
文章历史 +

摘要

目前对于程序性死亡因子1(PD1)在感染性疾病中对免疫调节的作用主要集中在慢性病毒感染相关的研究,而在急性病毒感染中研究较少。在慢性病毒感染中,PD1高表达于CD8+T细胞表面,这是CD8+T细胞耗竭的标志之一。最近研究显示,在慢性病毒感染中,也存在高表达于调节性T细胞表面的PD1,与耗竭CD8+T细胞表面PD1配体1(PD-L1)结合导致对CD8+T细胞免疫产生更强的抑制效应。阻断耗竭CD8+T细胞与调节性T细胞之间的PD1/PD-L1信号通路可以明显逆转耗竭CD8+T细胞功能,并极大改善耗竭CD8+T细胞抗病毒效应。然而,在急性病毒感染中,PD1/PD-L1信号通路的作用并不明确。本文主要概括了关于PD1在感染性疾病中最新的研究,并论述其在急性、慢性病毒感染中的作用。

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.

关键词

程序性死亡因子1 / 病毒感染 / 调节性T细胞 / 耗竭CD8+T细胞

Key words

Programmed death-1 / Viral infection / Regulatory T cell / Exhausted CD8+ T cell

引用本文

导出引用
陆富策, 农光民. 程序性死亡因子1在病毒感染性疾病中的作用[J]. 中国当代儿科杂志. 2018, 20(1): 77-82 https://doi.org/10.7499/j.issn.1008-8830.2018.01.016
LU Fu-Ce, NONG Guang-Min. Role of programmed death-1 in viral infectious diseases[J]. Chinese Journal of Contemporary Pediatrics. 2018, 20(1): 77-82 https://doi.org/10.7499/j.issn.1008-8830.2018.01.016

参考文献

[1] 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].

基金

国家自然科学基金(81460251);广西壮族自治区手足口病防治研究资金(2014249)。

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