The viral context instructs the redundancy of costimulatory pathways in driving CD8+ T cell expansion

被引:43
作者
Welten, Suzanne P. M. [1 ]
Redeker, Anke [1 ]
Franken, Kees L. M. C. [1 ]
Oduro, Jennifer D. [2 ]
Ossendorp, Ferry [1 ]
Cicin-Sain, Luka [2 ,3 ]
Melief, Cornelis J. M. [1 ,4 ]
Aichele, Peter [5 ]
Arens, Ramon [1 ]
机构
[1] Leiden Univ, Med Ctr, Dept Immunohematol & Blood Transfus, Leiden, Netherlands
[2] Helmholtz Zentrum Infekt Forsch GmbH, Dept Vaccinol Immune Aging & Chron Infect, Braunschweig, Germany
[3] Hannover Med Sch, Dept Virol, Hannover, Germany
[4] ISA Pharmaceut, Leiden, Netherlands
[5] Univ Freiburg, Dept Med Microbiol & Hyg, Inst Immunol, D-79106 Freiburg, Germany
来源
ELIFE | 2015年 / 4卷
关键词
LYMPHOCYTIC CHORIOMENINGITIS VIRUS; ANTIGEN-PRESENTING CELLS; TNFR FAMILY-MEMBERS; CLONAL EXPANSION; DENDRITIC CELLS; IN-VIVO; ANTIVIRAL IMMUNITY; MEMORY FORMATION; RECALL RESPONSE; DC SUBSETS;
D O I
10.7554/eLife.07486
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Signals delivered by costimulatory molecules are implicated in driving T cell expansion. The requirements for these signals, however, vary from dispensable to essential in different infections. We examined the underlying mechanisms of this differential T cell costimulation dependence and found that the viral context determined the dependence on CD28/B7-mediated costimulation for expansion of naive and memory CD8(+) T cells, indicating that the requirement for costimulatory signals is not imprinted. Notably, related to the high-level costimulatory molecule expression induced by lymphocytic choriomeningitis virus (LCMV), CD28/B7-mediated costimulation was dispensable for accumulation of LCMV-specific CD8(+) T cells because of redundancy with the costimulatory pathways induced by TNF receptor family members (i.e., CD27, OX40,and 4-1BB). Type I IFN signaling in viral-specific CD8(+) T cells is slightly redundant with costimulatory signals. These results highlight that pathogen-specific conditions differentially and uniquely dictate the utilization of costimulatory pathways allowing shaping of effector and memory antigen-specific CD8(+) T cell responses.
引用
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页数:20
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