CD27-CD70 Costimulation Controls T Cell Immunity during Acute and Persistent Cytomegalovirus Infection

被引:58
作者
Welten, Suzanne P. M. [1 ]
Redeker, Anke [1 ]
Franken, Kees L. [1 ]
Benedict, Chris A. [2 ]
Yagita, Hideo [3 ]
Wensveen, Felix M. [4 ,5 ]
Borst, Jannie [6 ]
Melief, Cornelis J. M. [1 ,7 ]
van Lier, Rene A. W. [6 ]
van Gisbergen, Klaas P. J. M. [6 ]
Arens, Ramon [1 ]
机构
[1] Leiden Univ, Med Ctr, Dept Immunohematol & Blood Transfus, Leiden, Netherlands
[2] La Jolla Inst Allergy & Immunol, Div Immune Regulat, La Jolla, CA USA
[3] Juntendo Univ, Sch Med, Dept Immunol, Tokyo 113, Japan
[4] Cent Lab Blood Transfus Serv, Sanquin Res, Dept Hematopoiesis, Amsterdam, Netherlands
[5] Landsteiner Lab, Amsterdam, Netherlands
[6] Netherlands Canc Inst, Div Immunol, NL-1066 CX Amsterdam, Netherlands
[7] ISA Therapeut, Leiden, Netherlands
关键词
LYMPHOCYTIC CHORIOMENINGITIS VIRUS; CHRONIC VIRAL-INFECTION; MURINE CYTOMEGALOVIRUS; MEMORY INFLATION; HUMAN CMV; CD27; EFFECTOR; MICE; DIFFERENTIATION; RESPONSES;
D O I
10.1128/JVI.03305-12
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Cytomegaloviruses (CMVs) establish lifelong infections that are controlled in part by CD4(+) and CD8(+) T cells. To promote persistence, CMVs utilize multiple strategies to evade host immunity, including modulation of costimulatory molecules on infected antigen-presenting cells. In humans, CMV-specific memory T cells are characterized by the loss of CD27 expression, which suggests a critical role of the costimulatory receptor-ligand pair CD27-CD70 for the development of CMV-specific T cell immunity. In this study, the in vivo role of CD27-CD70 costimulation during mouse CMV infection was examined. During the acute phase of infection, the magnitudes of CMV-specific CD4(+) and CD8(+) T cell responses were decreased in mice with abrogated CD27-CD70 costimulation. Moreover, the accumulation of inflationary memory T cells during the persistent phase of infection and the ability to undergo secondary expansion required CD27-CD70 interactions. The downmodulation of CD27 expression, however, which occurs gradually and exclusively on inflationary memory T cells, is ligand independent. Furthermore, the IL-2 production in both noninflationary and inflationary CMV-specific T cells was dependent on CD27-CD70 costimulation. Collectively, these results highlight the importance of the CD27-CD70 costimulation pathway for the development of CMV-specific T cell immunity during acute and persistent infection.
引用
收藏
页码:6851 / 6865
页数:15
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