Inverse correlation between IL-7 receptor expression and CD8 T cell exhaustion during persistent antigen stimulation

被引：153

作者：

Lang, KS ^{[1
]}

Recher, M ^{[1
]}

Navarini, AA ^{[1
]}

Harris, NL ^{[1
]}

Löhning, M ^{[1
]}

Junt, T ^{[1
]}

Probst, HC ^{[1
]}

Hengartner, H ^{[1
]}

Zinkernagel, RM ^{[1
]}

机构：

[1] Inst Expt Immunol, CH-8091 Zurich, Switzerland

来源：

EUROPEAN JOURNAL OF IMMUNOLOGY | 2005年 / 35卷 / 03期

关键词：

lymphocytic choriomeningitis virus; exhaustion; Bcl-2; persistence; re-emergence;

D O I：

10.1002/eji.200425828

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Persistence is a hallmark of infection by viruses such as HIV, hepatitis B virus, hepatitis C virus and LCMV. In the case of LCMV, persistence may often. be associated with exhaustion of CD8(+) T cells. We demonstrate here that persistent antigen suppressed IL-7R alpha expression and this correlated with T cell exhaustion and reduced expression of the anti-apoptotic molecule B cell leukemia/lymphoma 2 (Bcl-2). In contrast, exposure to short-lived antigen only temporarily suppressed IL-7R alpha expression, failed to induce T cell exhaustion, and primed Tcells. Persistent antigen also suppressed IL-7R alpha expression on primed T cells and this correlated with exhaustion of a previously stable primed T cell population. These findings suggest that antigen longevity regulates T cell fate.

引用

收藏

页码：738 / 745

页数：8

相关论文

共 30 条

[1] T-CELL PRIMING VERSUS T-CELL TOLERANCE INDUCED BY SYNTHETIC PEPTIDES [J].

AICHELE, P ;

BRDUSCHARIEM, K ;

ZINKERNAGEL, RM ;

HENGARTNER, H ;

PIRCHER, H .

JOURNAL OF EXPERIMENTAL MEDICINE, 1995, 182 (01) :261-266

[2] Bcl-2 rescues T lymphopoiesis in interleukin-7 receptor-deficient mice [J].

Akashi, K ;

Kondo, M ;

vonFreedenJeffry, U ;

Murray, R ;

Weissman, IL .

CELL, 1997, 89 (07) :1033-1041

[3] The role of caspase 3 and BclxL in the action of interleukin 7 (IL-7):: A survival factor in activated human T cells [J].

Amos, CL ;

Woetmann, A ;

Nielsen, M ;

Geisler, C ;

Odum, N ;

Brown, BL ;

Dobson, PRM .

CYTOKINE, 1998, 10 (09) :662-668

[4] HIV-specific CD8+ T cells produce antiviral cytokines but are impaired in cytolytic function [J].

Appay, V ;

Nixon, DF ;

Donahoe, SM ;

Gillespie, GMA ;

Dong, T ;

King, A ;

Ogg, GS ;

Spiegel, HML ;

Conlon, C ;

Spina, CA ;

Havlir, DV ;

Richman, DD ;

Waters, A ;

Easterbrook, P ;

McMichael, AJ ;

Rowland-Jones, SL .

JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 192 (01) :63-75

[5]

CHISARI FV, 1995, ANNU REV IMMUNOL, V13, P29, DOI 10.1146/annurev.iy.13.040195.000333

[6] Persistence of lymphocytic choriomeningitis virus at very low levels in immune mice [J].

Ciurea, A ;

Klenerman, P ;

Hunziker, L ;

Horvath, E ;

Odermatt, B ;

Ochsenbein, AF ;

Hengartner, H ;

Zinkernagel, RM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (21) :11964-11969

[7] The tumoricidal activity of memory CD8+ T cells is hampered by persistent systemic antigen, but full functional capacity is regained in an antigen-free environment [J].

den Boer, AT ;

van Mierlo, GJD ;

Fransen, MF ;

Melief, CJM ;

Offringa, R ;

Toes, REM .

JOURNAL OF IMMUNOLOGY, 2004, 172 (10) :6074-6079

[8] Induction and exhaustion of lymphocytic choriomeningitis virus-specific cytotoxic T lymphocytes visualized using soluble tetrameric major histocompatibility complex class I peptide complexes [J].

Gallimore, A ;

Glithero, A ;

Godkin, A ;

Tissot, AC ;

Plückthun, A ;

Elliott, T ;

Hengartner, H ;

Zinkernagel, R .

JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 187 (09) :1383-1393

[9]

HERNANDEZCASELLES, 1995, HUM IMMUNOL, V43, P181

[10] Selective expression of the interleukin 7 receptor identifies effector CD8 T cells that give rise to long-lived memory cells [J].

Kaech, SM ;

Tan, JT ;

Wherry, EJ ;

Konieczny, BT ;

Surh, CD ;

Ahmed, R .

NATURE IMMUNOLOGY, 2003, 4 (12) :1191-1198