Intrinsic versus environmental influences on T-cell responses in aging

A decline in T‐cell responses and a switch to memory T‐cell predominance occur with aging. We have used the T‐cell receptor (TCR) transgenic mouse model to study age‐associated changes in T‐cell responses that are a consequence of shifts in subset representation versus changes intrinsic to T cells v...

Full description

Saved in:
Bibliographic Details
Published in:Immunological reviews 2005-06, Vol.205 (1), p.207-219
Main Authors: Linton, Phyllis-Jean, Li, Shaokang P., Zhang, Yu, Bautista, Beverly, Huynh, Quan, Trinh, Tan
Format: Article
Language:English
Subjects:
Aging - immunology
Animals
Antigens - immunology
Cell Proliferation
Environment
Humans
Receptors, Antigen, T-Cell - immunology
T-Lymphocytes - cytology
T-Lymphocytes - immunology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:A decline in T‐cell responses and a switch to memory T‐cell predominance occur with aging. We have used the T‐cell receptor (TCR) transgenic mouse model to study age‐associated changes in T‐cell responses that are a consequence of shifts in subset representation versus changes intrinsic to T cells versus changes in the ‘aged’ microenvironment. We found that naive transgene‐expressing (Tg+) CD4+ T cells from aged mice respond to antigen with reduced interleukin‐2 (IL‐2) production, decreased cell expansion, and limited differentiation to effectors. Comparable to the characteristic accumulation of memory phenotype T cells in aged humans and conventional rodents, Tg+ CD4+ T cells from old OTII and 6.5 TCR transgenic mice acquire a memory phenotype without immunization and become hyporesponsive. The naive Tg+ CD8+ T cells from aged 2C mice expressed activation markers, produced IL‐2, proliferated, and differentiated into cytotoxic T lymphocytes as efficiently as their young counterparts. Responses by adoptive transferred Tg+ cells from young mice, immunized in young and old conventional hosts, indicated that the host age influences the onset of cell division, level of cell expansion, and number of cytokine‐producing cells. Co‐transfer of dendritic cells (DCs) from young and less so from aged conventional mice partially restored responses. Furthermore, DCs and T‐cell migration to draining lymphoid organs was reduced due to deficiencies intrinsic to aged cells and the aged environment. Thus, alterations in T‐cell responses in aging are attributable to intrinsic and environmental influences.
ISSN:0105-2896
1600-065X
DOI:10.1111/j.0105-2896.2005.00266.x