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Age-associated increase of low-avidity cytomegalovirus-specific CD8+ T cells that re-express CD45RA.

Age-associated increase of low-avidity cytomegalovirus-specific CD8+ T cells that re-express CD45RA.

Authors :
Griffiths SJ
Riddell NE
Masters J
Libri V
Henson SM
Wertheimer A
Wallace D
Sims S
Rivino L
Larbi A
Kemeny DM
Nikolich-Zugich J
Kern F
Klenerman P
Emery VC
Akbar AN
Source :
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2013 Jun 01; Vol. 190 (11), pp. 5363-72. Date of Electronic Publication: 2013 May 01.
Publication Year :
2013

Abstract

The mechanisms regulating memory CD8(+) T cell function and homeostasis during aging are unclear. CD8(+) effector memory T cells that re-express CD45RA increase considerably in older humans and both aging and persistent CMV infection are independent factors in this process. We used MHC class I tetrameric complexes that were mutated in the CD8 binding domain to identify CMV-specific CD8(+) T cells with high Ag-binding avidity. In individuals who were HLA-A*0201, CD8(+) T cells that expressed CD45RA and were specific for the pp65 protein (NLVPMVATV epitope) had lower avidity than those that expressed CD45RO and demonstrated decreased cytokine secretion and cytolytic potential after specific activation. Furthermore, low avidity NLVPMVATV-specific CD8(+) T cells were significantly increased in older individuals. The stimulation of blood leukocytes with CMV lysate induced high levels of IFN-α that in turn induced IL-15 production. Moreover, the addition of IL-15 to CD45RA(-)CD45RO(+) CMV-specific CD8(+) T cells induced CD45RA expression while Ag activated cells remained CD45RO(+). This raises the possibility that non-specific cytokine-driven accumulation of CMV-specific CD8(+)CD45RA(+) T cells with lower Ag-binding avidity may exacerbate the effects of viral reactivation on skewing the T cell repertoire in CMV-infected individuals during aging.

Details

Language :
English
ISSN :
1550-6606
Volume :
190
Issue :
11
Database :
MEDLINE
Journal :
Journal of immunology (Baltimore, Md. : 1950)
Publication Type :
Academic Journal
Accession number :
23636061
Full Text :
https://doi.org/10.4049/jimmunol.1203267