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Trudeau Institute, Saranac Lake, NY 12983
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 Vβ5+ 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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Public Health Service Grants AGO25805, AGO21600 PR1, and F32 AGO27641 (to S.J.) and by Trudeau Institute.
2 Address correspondence and reprint requests to Dr. Susan L. Swain, Trudeau Institute, 154 Algonquin Avenue, Saranac Lake, NY, 12983. E-mail address: sswain{at}trudeauinstitute.org
3 Abbreviations used in this paper: Tg, transgenic; RTE, recent thymic emigrant; SAg, superantigen; Mtv, mouse mammary tumor virus; HA, hemagglutinin; KO, knockout; ICCS, intracellular cytokine staining; MFI, mean fluorescence intensity.
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