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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Sims, Stuart Rivino, Laura Larbi, Anis Henson, Sian M. Emery, Vince C. Akbar, Arne N. Klenerman, Paul Wallace, Diana Wertheimer, Anne Masters, Joanne Libri, Valentina Griffiths, Stephen J. Kemeny, David M. Riddell, Natalie E. Nikolich-Zugich, Janko Kern, Florian |
| Description | Country affiliation: United kingdom Author Affiliation: Griffiths SJ ( Division of Infection and Immunity, University College London, London WC1E 6BT, United Kingdom.) |
| 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- 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. |
| ISSN | 00221767 |
| e-ISSN | 15506606 |
| DOI | 10.4049/jimmunol.1203267 |
| Journal | The Journal of Immunology |
| Issue Number | 11 |
| Volume Number | 190 |
| Language | English |
| Publisher | The American Association of Immunologists |
| Publisher Date | 2013-06-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Antigens, Cd45 Metabolism Cd8-positive T-lymphocytes Immunology Cytomegalovirus Infections Cytomegalovirus Antibody Affinity Antigens Dendritic Cells Hla-a2 Antigen Immunophenotyping Interferon-alpha Biosynthesis Interleukin-15 Lymphocyte Activation Monocytes Phosphoproteins Viral Matrix Proteins Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
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