Competition between T cells maintains clonal dominance during memory inflation induced by MCMV

被引:27
作者
Turula, Holly [1 ]
Smith, Corinne J. [1 ]
Grey, Finn [2 ,3 ]
Zurbach, Katherine A. [1 ]
Snyder, Christopher M. [1 ]
机构
[1] Thomas Jefferson Univ, Kimmel Canc Ctr, Jefferson Med Coll, Dept Microbiol & Immunol, Philadelphia, PA 19107 USA
[2] Univ Edinburgh, Roslin Inst, Easter Bush, Midlothian, Scotland
[3] Univ Edinburgh, Royal Dick Sch Vet Studies, Easter Bush, Midlothian, Scotland
关键词
CD8+T cells; Memory cells; Immune responses; MURINE CYTOMEGALOVIRUS-INFECTION; BONE-MARROW-TRANSPLANTATION; SELECTION; AFFINITY; ANTIGEN; ENGRAFTMENT; RESPONSES; IMMUNITY; RECONSTITUTION; POPULATIONS;
D O I
10.1002/eji.201242940
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Both human cytomegalovirus (HCMV) and murine cytomegalovirus (MCMV) establish persistent infections that induce the accumulation of virus-specific T cells over time in a process called memory inflation. It has been proposed that T cells expressing T-cell receptors (TCRs) with high affinity for HCMV-derived peptides are preferentially selected after acute HCMV infection. To test this in the murine model, small numbers of OT-I transgenic T cells, which express a TCR with high affinity for the SIINFEKL peptide, were transferred into congenic mice and recipients were challenged with recombinant MCMV expressing SIINFEKL. OT-I T cells were selectively enriched during the first 3 weeks of infection. Similarly, in the absence of OT-I T cells, the functional avidity of SIINFEKL-specific T cells increased from early to late times postinfection. However, even when exceedingly small numbers of OT-I T cells were transferred, their inflation limited the inflation of host-derived T cells specific for SIINFEKL. Importantly, subtle minor histocompatibility differences led to late rejection of the transferred OT-I T cells in some mice, which allowed host-derived T cells to inflate substantially. Thus, T cells with a high functional avidity are selected shortly after MCMV infection and continuously sustain their clonal dominance in a competitive manner.
引用
收藏
页码:1252 / 1263
页数:12
相关论文
共 41 条
[1]   T-cell-receptor affinity and thymocyte positive selection [J].
Alam, SM ;
Travers, PJ ;
Wung, JL ;
Nasholds, W ;
Redpath, S ;
Jameson, SC ;
Gascoigne, NRJ .
NATURE, 1996, 381 (6583) :616-620
[2]   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
[3]   Endogenous naive CD8+ T cell precursor frequency regulates primary and memory responses to infection [J].
Bar, Joshua J. ;
Khanna, Kamal M. ;
Lefrancois, Leo .
IMMUNITY, 2008, 28 (06) :859-869
[4]   Purified hematopoietic stem cell engraftment of rare niches corrects severe lymphoid deficiencies without host conditioning [J].
Bhattacharya, D ;
Rossi, DJ ;
Bryder, D ;
Weissman, IL .
JOURNAL OF EXPERIMENTAL MEDICINE, 2006, 203 (01) :73-85
[5]  
Chen W, 1998, J IMMUNOL, V161, P909
[6]   T cell acquisition of APC membrane can impact interpretation of adoptive transfer experiments using CD45 congenic mouse strains [J].
Cho, Kathy S. ;
Hill, Ann B. .
JOURNAL OF IMMUNOLOGICAL METHODS, 2008, 330 (1-2) :137-145
[7]   Immunobiology of Human Cytomegalovirus: from Bench to Bedside [J].
Crough, Tania ;
Khanna, Rajiv .
CLINICAL MICROBIOLOGY REVIEWS, 2009, 22 (01) :76-+
[8]   Promoter control over foreign antigen expression in a murine cytomegalovirus vaccine vector [J].
Cunningham, Paula T. ;
Lloyd, Megan L. ;
Harvey, Nicole L. ;
Williams, Elizabeth ;
Hardy, Christopher M. ;
Redwood, Alec J. ;
Lawson, Malcolm A. ;
Shellam, Geoffrey R. .
VACCINE, 2010, 29 (01) :141-151
[9]   Rapid CD8+ T cell repertoire focusing and selection of high-affinity clones into memory following primary infection with a persistent human virus:: Human Cytomegalovirus [J].
Day, Elizabeth K. ;
Carmichael, Andrew J. ;
Ten Berge, Ineke J. M. ;
Waller, Edward C. P. ;
Sissons, J. G. Patrick ;
Wills, Mark R. .
JOURNAL OF IMMUNOLOGY, 2007, 179 (05) :3203-3213
[10]   The Immunological Impact of Genetic Drift in the B10.BR Congenic Inbred Mouse Strain [J].
Fanning, Stacey L. ;
Appel, Michael Y. ;
Berger, Stephanie A. ;
Korngold, Robert ;
Friedman, Thea M. .
JOURNAL OF IMMUNOLOGY, 2009, 183 (07) :4261-4272