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 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.
Linton
Phyllis-Jean
PJ
Sidney Kimmel Cancer Center, San Diego, CA 92121, USA. plinton@skcc.org
Li
Shaokang P
SP
Zhang
Yu
Y
Bautista
Beverly
B
Huynh
Quan
Q
Trinh
Tan
T
D000375:Aging / Q000276:immunology*; D000818:Animals; D000941:Antigens / Q000276:immunology; D049109:Cell Proliferation; D004777:Environment; D006801:Humans; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D000941:Antigens; D011948:Receptors, Antigen, T-Cell