2004
DOI: 10.1084/jem.20040437
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Age-related CD8 T Cell Clonal Expansions Constrict CD8 T Cell Repertoire and Have the Potential to Impair Immune Defense

Abstract: Peripheral T cell diversity is virtually constant in the young, but is invariably reduced in aged mice and humans. CD8+ T cell clonal expansions (TCE) are the most drastic manifestation of, and possible contributors to, this reduced diversity. We show that the presence of TCE results in reduced CD8+, but not CD4+, T cell diversity, and in functional inability to mobilize parts of the CD8+ T cell repertoire affected by TCE. In the model of herpes simplex virus (HSV)-1 infection of B6 mice, >90% of the respondin… Show more

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Cited by 214 publications
(182 citation statements)
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“…For example, IL-7 is believed to be the main regulator of N T cell turnover, and its administration to monkeys has been shown to increase N T cell proliferation (28). Based on our recent findings (19,29,30), the reduction in naïve T cell representation and diversity resulting from a mechanism of this kind would have the potential to adversely affect the induction of protective immunity.…”
Section: Discussionmentioning
confidence: 99%
“…For example, IL-7 is believed to be the main regulator of N T cell turnover, and its administration to monkeys has been shown to increase N T cell proliferation (28). Based on our recent findings (19,29,30), the reduction in naïve T cell representation and diversity resulting from a mechanism of this kind would have the potential to adversely affect the induction of protective immunity.…”
Section: Discussionmentioning
confidence: 99%
“…First, in humans, there are correlative data indicating that individuals with clonal expansions are less likely to respond successfully to an influenza vaccination (Saurwein-Teissl et al, 2002). Second, in mice, there are data that the presence of CD8 clonal expansions may result in very narrow holes in the T cell repertoire, which in some circumstances may impair immune responses to pathogens (Messaoudi et al, 2004). While these data indicate that clonal expansions may contribute to age-dependent immune compromise, it is important to note that affected individuals are not generally immune-suppressed.…”
Section: Impact Of Cd8 Clonal Expansions On Immune Function and Healthmentioning
confidence: 99%
“…clonality & increased competitive advantage relative to their neighbors), CD8 clonal expansions are clearly not tumors. First, individuals with expansions have no change in the total number of CD8 T cells (Messaoudi et al, 2004). Second, individuals (both humans and mice) live healthy lives with clonal expansions (Chamberlain et al, 2000), and the incidence of CD8 memory T cell tumors in humans is exceedingly rare.…”
Section: Impact Of Cd8 Clonal Expansions On Immune Function and Healthmentioning
confidence: 99%
“…For example, aged humans with TCEs are less likely to respond successfully to influenza vaccination (7). Moreover, studies in mice indicate that the presence of TCEs may result in narrow holes in the T cell repertoire that, in some cases, may result in poor responses to pathogens that elicit a highly focused T cell response (6). TCEs are not tumors and do not appear to progress to malignancy over at least nine years (8).…”
mentioning
confidence: 99%
“…TCEs vary in size but can occupy a large portion of the total CD8 T cell pool (up to 50% in humans, up to 90% in mice) (unpublished data) (5). Individuals with TCEs have no change in the total number of CD8 T cells (6).…”
mentioning
confidence: 99%