Is immunosenescence infectious?

被引:176
作者
Pawelec, G
Akbar, A
Caruso, C
Effros, R
Grubeck-Loebenstein, B
Wikby, A
机构
[1] Univ Tubingen, Sch Med, Med Res Ctr, ZMF, D-72072 Tubingen, Germany
[2] UCL Royal Free & Univ Coll Med Sch, Windeyer Inst Med Sci, Dept Immunol & Mol Pathol, London W1T 4JF, England
[3] Univ Palermo, Dipartimento Biopatol & Metedol Biomed, Grp Studio Immunosenescenza, I-90134 Palermo, Italy
[4] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA
[5] Austrian Acad Sci, Inst Biomed Ageing Res, Div Immunol, A-6020 Innsbruck, Austria
[6] Jonkoping Univ, Sch Hlth Sci, Dept Nat Sci & Biomed, SE-55111 Jonkoping, Sweden
关键词
D O I
10.1016/j.it.2004.05.006
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Herpes viruses are endemic. Once established, the virus is never eliminated but persists throughout life. The fraction of infected individuals gradually increases with age, such that the majority of elderly people are cytomegalovirus (CMV)(+), Epstein-Barr virus (EBV)(+) and Varicella(+). Clinically relevant reactivation of Varicella causes painful shingles; CMV reactivation can cause fatal pneumonia. Overt reactivation, even in the very elderly, occurs only in immunocompromised individuals; however, the necessity for maintaining immunity to these viruses is costly. We argue that this cost is not only reflected in the requirement for continuous immunosurveillance against these viruses but, more importantly, results in a re-configuration of T-cell immunity due to the accumulation of dysfunctional virus-specific cells, which fail to be eliminated from the system. Thus, we hypothesize that it is the chronic antigenic stimulation by CMV (and possibly other persisting antigens) that leads to an increasing prevalence of senescent, dysfunctional T cells, and therefore contributes to more general alterations in the immune system, which are associated with earlier mortality.
引用
收藏
页码:406 / 410
页数:5
相关论文
共 42 条
[1]   Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infections [J].
Appay, V ;
Dunbar, PR ;
Callan, M ;
Klenerman, P ;
Gillespie, GMA ;
Papagno, L ;
Ogg, GS ;
King, A ;
Lechner, F ;
Spina, CA ;
Little, S ;
Havlir, DV ;
Richman, DD ;
Gruener, N ;
Pape, G ;
Waters, A ;
Easterbrook, P ;
Salio, M ;
Cerundolo, V ;
McMichael, AJ ;
Rowland-Jones, SL .
NATURE MEDICINE, 2002, 8 (04) :379-385
[2]  
APPERLEY JF, 1988, BONE MARROW TRANSPL, V3, P253
[3]   Oligoclonal expansions in the CD8+CD28- T cells largely explain the shorter telomeres detected in this subset:: Analysis by flow FISH [J].
Batliwalla, FM ;
Rufer, N ;
Lansdorp, PM ;
Gregersen, PK .
HUMAN IMMUNOLOGY, 2000, 61 (10) :951-958
[4]   Effect of previous or simultaneous immunization with canarypox expressing cytomegalovirus (CMV) glycoprotein B (gB) on response to subunit gB vaccine plus MF59 in healthy CMV-seronegative adults [J].
Bernstein, DI ;
Schleiss, MR ;
Berencsi, K ;
Gonczol, E ;
Dickey, M ;
Khoury, P ;
Cadoz, M ;
Meric, C ;
Zahradnik, J ;
Duliege, AM ;
Plotkin, S .
JOURNAL OF INFECTIOUS DISEASES, 2002, 185 (05) :686-690
[5]   Immunogenetics of longevity.: Is major histocompatibility complex polymorphism relevant to the control of human longevity?: A review of literature data [J].
Caruso, C ;
Candore, G ;
Romano, GC ;
Lio, D ;
Bonafè, M ;
Valensin, S ;
Franceschi, C .
MECHANISMS OF AGEING AND DEVELOPMENT, 2001, 122 (05) :445-462
[6]   CD8+CD28- T suppressor cells and the induction of antigen-specific, antigen-presenting cell-mediated suppression of Th reactivity [J].
Cortesini, R ;
LeMaoult, J ;
Ciubotariu, R ;
Cortesini, NSF .
IMMUNOLOGICAL REVIEWS, 2001, 182 :201-206
[7]   Differential impairment of lytic and cytokine functions in senescent human immunodeficiency virus type 1-specific cytotoxic T lymphocytes [J].
Dagarag, M ;
Ng, H ;
Lubong, R ;
Effros, RB ;
Yang, OO .
JOURNAL OF VIROLOGY, 2003, 77 (05) :3077-3083
[8]   Epstein-Barr virus-specific CD8+ T cells that re-express CD45RA are apoptosis-resistant memory cells that retain replicative potential [J].
Dunne, PJ ;
Faint, JM ;
Gudgeon, NH ;
Fletcher, JM ;
Plunkett, FJ ;
Scares, MVD ;
Hislop, AD ;
Annels, NE ;
Rickinson, AB ;
Salmon, M ;
Akbar, AN .
BLOOD, 2002, 100 (03) :933-940
[9]   DECLINE IN CD28(+) T-CELLS IN CENTENARIANS AND IN LONG-TERM T-CELL CULTURES - A POSSIBLE CAUSE FOR BOTH IN-VIVO AND IN-VITRO IMMUNOSENESCENCE [J].
EFFROS, RB ;
BOUCHER, N ;
PORTER, V ;
ZHU, XM ;
SPAULDING, C ;
WALFORD, RL ;
KRONENBERG, M ;
COHEN, D ;
SCHACHTER, F .
EXPERIMENTAL GERONTOLOGY, 1994, 29 (06) :601-609
[10]   Replicative senescence of T cells: does the Hayflick Limit lead to immune exhaustion? [J].
Effros, RB ;
Pawelec, G .
IMMUNOLOGY TODAY, 1997, 18 (09) :450-454