T-cell dysregulation caused by chronic antigenic stress: the role of CMV in immunosenescence?
Dysfunctional T-cell immunity contributes to susceptibility to infectious disease in the elderly. A characteristic feature of this "immunosenescence" is the predominance of clonal expansions of CD8 cells and decreased diversity of the T-cell antigen receptor repertoire. Lifelong chronic antigenic stress commonly caused by infection with persistent activating herpes viruses causes the accumulation of anergic, apoptosis-resistant CD8 T cells. These dysfunctional cells are indirectly immunosuppressive by tasking up the "immunological space" as well as directly suppressive via blockade of antigen presenting cells or cytokine secretion. They are associated with an emerging "immunological risk profile" predicting mortality in longitudinal studies of very old people. It is therefore hypothesized that for that majority of elderly people infected with cytomegalovirus (CMV), which seems to act as the dominant chronic stressor, anti-viral strategies would be of benefit in abrogating some of the detrimental clinical manifestations of immunosenescence.
Pawelec
Graham
G
Center for Medical Research, University of Tübingen, Germany. graham.pawelec@uni-tuebingen.de
Gouttefangeas
Cécile
C
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology*; D000951:Antigens, Neoplasm; D000956:Antigens, Viral; D015551:Autoimmunity; D015704:CD4 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes; D016827:CD8 Antigens; D018414:CD8-Positive T-Lymphocytes; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000503:physiopathology; D004198:Disease Susceptibility / Q000276:immunology / Q000503:physiopathology; D006801:Humans; D007165:Immunosuppression Therapy; D009369:Neoplasms / Q000276:immunology; D013312:Stress, Physiological / Q000276:immunology*; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology*
D000951:Antigens, Neoplasm; D000956:Antigens, Viral; D015704:CD4 Antigens; D016827:CD8 Antigens