Impact of post-thymic cellular longevity on the development of age-associated CD4+ T cell defects.
Elderly people are at higher risk for infections due to declining cellular and humoral immune responses. Central to this dysfunction is the reduced responsiveness of the naive CD4(+) T cell compartment. Previous data from our laboratory suggest that although defects in the aged naive CD4(+) T cell response are apparent in recent thymic emigrant populations, additional defects develop during extended post-thymic longevity in the periphery. To further investigate the factors that lead to aging defects, we took advantage of the OT-II TCR-transgenic (Tg) mouse model. We show that because of an apparent superantigen-mediated loss of naive Vbeta5(+) Tg CD4(+) T cells from the periphery of aging OT-II mice, this compartment becomes enriched for cells of reduced post-thymic longevity, resulting in a frequency of recent thymic emigrants in aged mice that is similar to that of young mice. Purification and functional analysis of aged OT-II cells with reduced post-thymic longevity reveal that they have an age-associated decrease in expansion and IL-2 production in response to Ag in vitro. However, the in vivo expansion, IL-2 production, and cognate B cell helper ability of these cells are similar to those of cells from young mice. In contrast, T cells from aged HNT Tg mice demonstrate extended post-thymic longevity and exhibit severe defects in the same in vitro and in vivo models. These data support a correlation between the requirement for increased post-thymic longevity and the development of the most severe naive CD4(+) T cell-aging defects.
Jones
Stephen C
SC
Trudeau Institute, Saranac Lake, NY 12983, USA.
Clise-Dwyer
Karen
K
Huston
Gail
G
Dibble
John
J
Eaton
Sheri
S
Haynes
Laura
L
Swain
Susan L
SL
D000818:Animals; D000941:Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology*; D013997:Time Factors
D000941:Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta