The immunosuppression of lymphocyte activation gene 3 and its effects in chronic viral infection

doi:10.3969/j.issn.1673-8640.2015.03.026

Abstract

Abstract:

T cell depletion is the main mechanism that T cell responses can not effectively control viral replication and eliminate virus. Lymphocyte activation gene 3 (LAG-3) is a vital immune co-inhibitory molecule which is similar to CD4 molecule structure and mainly expresses on activated T cells. LAG-3 can be combined with major histocompability complex (MHC)-Ⅱ molecules, and it's also a negative regulator of T lymphocyte's proliferation and function for maintaining the homeostasis. LAG-3 highly expresses on the surface of virus-specific T cells causing T cell depletion in chronic viral infection.

Key words: Lymphocyte activation gene 3, T cell, Chronic viral infection, Depletion

CLC Number:

R446.62

MA Chenyun, LU Zhicheng, SHEN Qian. The immunosuppression of lymphocyte activation gene 3 and its effects in chronic viral infection[J]. Laboratory Medicine, 2015, 30(3): 298-302.

References 29

[1]	TRIEBEL F, JITSUKAWA S, BAIXERAS E, et al. LAG-3, a novel lymphocyte activation gene closely related to CD4[J]. J Exp Med, 1990,171(5):1393-1405.
[2]	BAIXERAS E, HUARD B, MIOSSEC C, et al. Characterization of the lymphocyte activation gene 3-encoded protein. A new ligand for human leukocyte antigen class Ⅱ antigens[J]. J Exp Med, 1992,176(2):327-337.
[3]	WORKMAN CJ, DUGGER KJ, VIGANLI DA. Cutting edge: molecular analysis of the negative regulatory function of lymphocyte activation gene-3[J]. J Immunol, 2002,169(10):5392-5495.
[4]	LI N, WORKMAN CJ, MARTIN SM, et al. Biochemical analysis of the regulatory T cell protein lymphocyte activation gene-3(LAG-3; CD223)[J]. J Immunol, 2004,173(11):6806-6812.
[5]	WORKMAN CJ, WANG Y, EL KASMIC KC, et al. LAG-3 regulates plassmacytoid dendritic cell homeostasis[J]. J Immunol, 2009,182(4):1885-1891.
[6]	BRUNIQUEL D, BORIE N, HANNIER S, et al. Regulation of expression of the human lymphocyte activation gene-3(LAG-3) molecule, a ligand for MHC class Ⅱ[J]. Immunogenetics, 1998,48(2):116-124.
[7]	LI N, WANG Y, FORBES K, et al. Metalloproteases regulate T-cell proliferation and effector function via LAG-3[J]. EMBO J, 2007,26(2):494-504.
[8]	TRIBEL F, HACENE K, PICHON MF. A soluble lymphocyte activation gene-3(sLAG-3) protein as a prognostic factor in human breast cancer expression estrogen or progesterone receptors[J]. Cancer Lett, 2006,235(1):147-153.
[9]	[9] LIENHARDT C, AZZURRI A, AMEDEI A, et al. Active tuberculosis in Africa is associated with reduced Th1 and increased Th2 activity in vivo[J]. Eur J Immunol, 2002,32(6):1605-1613.
[10]	遆新宇, 吴昌归, 陈卫强, 等. LAG-3-Ig对过敏性哮喘小鼠的Th1/Th2型细胞因子水平和气道反应性的影响[J]. 细胞与分子免疫学杂志, 2007,23(6):541-542.
[11]	HANNIER S, TOURNIER M, BISMUTH G, et al.CD3/TCR complex-associated lymphocyte activation gene-3 molecules inhibit CD3/TCR signaling[J]. J Immunol, 1998,161(8):4058-4065.
[12]	WORKMAN CJ, VIGNALI DA.Negative regulation of T cell homeostasis by lymphocyte activation gene-3(CD223)[J]. J Immunol, 2005,74(2):688-695.
[13]	WOO SR, LI N, BRUNO TC, et al.Differential subcellular localization of the regulatory T-cell protein LAG-3 and the coreceptor CD4[J]. Eur J Immunol, 2010,40(6):1768-1777.
[14]	GANDHI MK, LAMBLEY E, DURAISWAMY J, et al.Expression of LAG-3 by tumor infiltrating lymphocytes is coincident with the suppression of latent membrane antigen-specific CD8+ T-cell function in Hodgkin lymphoma patients[J]. Blood, 2006,108(7):2280-2289.
[15]	LIANG B, WORKMAN C, LEE J, et al.Regulatory T cells inhibit dendritic cells by lymphocyte activation gene-3 engagement of MHC class Ⅱ[J]. J Immunol, 2008,180(9):5916-5926.
[16]	GROSSO JF, KELLEHER CC, HARRIS TJ, et al.LAG-3 regulates CD8+ T cell accumulation and effector function in murine self-and tumor-tolerance systems[J]. J Clin Invest, 2007,117(11):3383-3392.
[17]	LUCAS CL, WORKMAN CJ, BEYAZ S, et al.LAG-3, TGF-β, and cell-intrinsic PD-1 inhibitory pathways contribute to CD8 but not CD4 T-cell tolerance induced by allogenic BMT with anti-CD40L[J]. Blood, 2011,117(20):5532-5540.
[18]	田晓玲, 仇超, 徐建青, 等. LAG-3分子与免疫调节[J]. 中华微生物学和免疫学杂志, 2013,33(3):231-236.
[19]	RICHTER K, AGNELLINI P, OXENIUS A.On the role of the inhibitory receptor LAG-3 in acute and chronic LCMV infection[J]. Int Immunol, 2010,22(1):13-23.
[20]	BLACKBURN SD, SHIN H, HAINING WN, et al.Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection[J]. Nat Immunol, 2009,10(1):29-37.
[21]	KHAITAN A, UNUTMAZ D.Revisiting immune exhaustion during HIV infection[J]. Curr HIV/AIDS Rep, 2011,8(1):4-11.
[22]	SHANKAR EM, CHE KF, MESSMER D, et al.Expression of a broad array of negative costimulatory molecules and Blimp-1 in T cells following priming by HIV-1 pulsed dendritic cells[J]. Mol Med, 2011,17(3-4):229-240.
[23]	ANTONELLI LR, MAHNKE Y, HODGE JN, et al.Elevated frequencies of highly activated CD4+ T cells in HIV+ patients developing immune reconstitution inflammatory syndrome[J]. Blood, 2010,116(19):3818-3827.
[24]	PEÑA J, JONES NG, BOUSHERI S, et al. Lymphocyte activation gene-3 expression defines a discrete subset of HIV-specific CD8+ T cells that is associated with lower viral load[J]. AIDS Res Hum Retroviruses, 2014,30(6):535-541.
[25]	SEUNG E, DUDEK TE, ALLEN TM, et al.PD-1 blockade in chronically HIV-1-infected humanized mice suppresses viral loads[J]. PLoS One, 2013,8(10):e77780.
[26]	LARSSON M, SHANKAR EM, CHE KF, et al.Molecular signatures of T-cell inhibition in HIV-1 infection[J]. Retrovirology, 2013,10:31.
[27]	LI FJ, ZHANG Y, JIN GX, et al.Expression of LAG-3 is coincident with the impaired effector function of HBV-specific CD8(+) T cell in HCC patients[J]. Immunol Lett, 2013,150(1-2):116-122.
[28]	KENNEDY PT, SANDALOVA E, JO J, et al.Preserved T-cell function in children and young adults with immune-tolerant chronic hepatitis B[J]. Gastroenterology, 2012,143(3):637-645.
[29]	KROY DC, CIUFFREDA D, COOPERRIDER JH, et al.Liver environment and HCV replication affect human T-cell phenotype and expression of inhibitory receptors[J]. Gastroenterology, 2014,146(2):550-561.