Homeostatic Turnover of Virus-Specific Memory CD8 T Cells Occurs Stochastically and Is Independent of CD4 T Cell Help

被引:45
作者
Choo, Daniel K. [1 ]
Murali-Krishna, Kaja [3 ,4 ]
Anita, Rustom [2 ]
Ahmed, Rafi [1 ]
机构
[1] Emory Univ, Dept Microbiol & Immunol, Emory Vaccine Ctr, Sch Med, Atlanta, GA 30322 USA
[2] Emory Univ, Dept Biol, Atlanta, GA 30322 USA
[3] Univ Washington, Dept Immunol, Sch Med, Seattle, WA 98195 USA
[4] Univ Washington, Sch Med, Washington Natl Primate Ctr, Seattle, WA 98195 USA
基金
美国国家卫生研究院;
关键词
CHRONIC VIRAL-INFECTION; IN-VIVO; IMMUNOLOGICAL MEMORY; LINEAGE RELATIONSHIP; PROTECTIVE IMMUNITY; CD4-DEFICIENT MICE; CD8-T-CELL MEMORY; CD4-T-CELL HELP; DEFICIENT MICE; BONE-MARROW;
D O I
10.4049/jimmunol.1001421
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
071005 [微生物学]; 100108 [医学免疫学];
摘要
Memory CD8 T cells persist by Ag-independent homeostatic proliferation. To examine the dynamics of this cell turnover, we transferred lymphocytic choriomeningitis virus specific memory CD8 T cells into naive mice and analyzed their in vivo division kinetics longitudinally in individual recipients. Using mathematical modeling, we determined that proliferation of this stably maintained memory CD8 T cell population was homogeneous and stochastic with a small fraction of cells completing division at any given time with an intermitotic interval of 50 d. This homeostatic turnover was comparable between memory CD8 T cells of different viral epitope specificities and also the total memory phenotype (CD44(high)) CD8 T cells. It is well established that CD4 T cell help is critical for maintenance of CD8 T cells during chronic infections, but recent studies have suggested that CD4 T cell help is also required for maintenance of memory CD8 T cells following acute infections. Hence, we assessed the role of CD4 T cells in Ag-independent maintenance of memory CD8 T cells. Consistent with previous reports, we found that memory CD8 T cells declined when transferred into MHC class II-deficient mice. However, their numbers were maintained stably when transferred into CD4 T cell-deficient mice. Interestingly, their homeostatic proliferation, ability to make recall responses, and phenotype were independent of CD4 T cell help because none of these qualities were affected when memory CD8 T cells were transferred and maintained in either MHC class II- or CD4-deficient recipients. The Journal of Immunology, 2010, 185: 3436-3444.
引用
收藏
页码:3436 / 3444
页数:9
相关论文
共 56 条
[1]
Immunological memory and protective immunity: Understanding their relation [J].
Ahmed, R ;
Gray, D .
SCIENCE, 1996, 272 (5258) :54-60
[2]
SELECTION OF GENETIC-VARIANTS OF LYMPHOCYTIC CHORIOMENINGITIS VIRUS IN SPLEENS OF PERSISTENTLY INFECTED MICE - ROLE IN SUPPRESSION OF CYTO-TOXIC LYMPHOCYTE-T RESPONSE AND VIRAL PERSISTENCE [J].
AHMED, R ;
SALMI, A ;
BUTLER, LD ;
CHILLER, JM ;
OLDSTONE, MBA .
JOURNAL OF EXPERIMENTAL MEDICINE, 1984, 160 (02) :521-540
[3]
Phenotypic analysis of antigen-specific T lymphocytes [J].
Altman, JD ;
Moss, PAH ;
Goulder, PJR ;
Barouch, DH ;
McHeyzerWilliams, MG ;
Bell, JI ;
McMichael, AJ ;
Davis, MM .
SCIENCE, 1996, 274 (5284) :94-96
[4]
Functional properties and lineage relationship of CD8+ T cell subsets identified by expression of IL-7 receptor α and CD62L [J].
Bachmann, MF ;
Wolint, P ;
Schwarz, K ;
Jäger, P ;
Oxenius, A .
JOURNAL OF IMMUNOLOGY, 2005, 175 (07) :4686-4696
[5]
Initial T cell receptor transgenic cell precursor frequency dictates critical aspects of the CD8+ T cell response to infection [J].
Badovinac, Vladimir P. ;
Haring, Jodie S. ;
Harty, John T. .
IMMUNITY, 2007, 26 (06) :827-841
[6]
Bone marrow is a preferred site for homeostatic proliferation of memory CD8 T cells [J].
Becker, TC ;
Coley, SM ;
Wherry, EJ ;
Ahmed, R .
JOURNAL OF IMMUNOLOGY, 2005, 174 (03) :1269-1273
[7]
Interleukin 15 is required for proliferative renewal of virus-specific memory CD8 T cells [J].
Becker, TC ;
Wherry, EJ ;
Boone, D ;
Murali-Krishna, K ;
Antia, R ;
Ma, A ;
Ahmed, R .
JOURNAL OF EXPERIMENTAL MEDICINE, 2002, 195 (12) :1541-1548
[8]
IL-15 promotes the survival of naive and memory phenotype CD8+ T cells [J].
Berard, M ;
Brandt, K ;
Paus, SB ;
Tough, DF .
JOURNAL OF IMMUNOLOGY, 2003, 170 (10) :5018-5026
[9]
Helping the CD8+ T-cell response [J].
Bevan, MJ .
NATURE REVIEWS IMMUNOLOGY, 2004, 4 (08) :595-602
[10]
Lineage relationships, homeostasis, and recall capacities of central- and effector-memory CD8 T cells in vivo [J].
Bouneauld, C ;
Garcia, Z ;
Kourilsky, P ;
Pannetier, C .
JOURNAL OF EXPERIMENTAL MEDICINE, 2005, 201 (04) :579-590