Age-related changes in naive and memory CD4+ T cells in healthy human children

Pirruccello, Samuel J.; Collins, Michaeleen; Wilson, Janet E.; McManus, Bruce M.

doi:10.1016/0090-1229(89)90185-2

Cited by 42 publications

(23 citation statements)

References 12 publications

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“…In accord with previous work in both mice and humans, [38][39][40] we found that aging is associated with a decreased production of naive T cells in both the CD4 ϩ and CD8 ϩ compartments (CD4 ϩ CD25 Ϫ CD44 Ϫ or CD8 ϩ CD112 Ϫ CD44 Ϫ ) and increased memory T cells (CD4 ϩ CD25 Ϫ CD44 ϩ or CD8 ϩ CD112 Ϫ CD44 ϩ ; Figure 3A), resulting in an increased ratio of memory/naive T cells with aging ( Figure 3B). T lineage-specific deletion of p16 INK4a , however, was For personal use only.…”

Section: Attenuation Of Immune Aging Phenotypes After Deletion Of P16supporting

confidence: 79%

Expression of p16INK4a prevents cancer and promotes aging in lymphocytes

Liu¹,

Johnson²,

Fedoriw

et al. 2011

Blood

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Previous authors have suggested that tumor suppressor expression promotes aging while preventing cancer, but direct experimental support for this canceraging hypothesis has been elusive. Here, by using somatic, tissue-specific inactivation of the p16 INK4a IntroductionAntagonistic pleiotropy, one of the oldest hypotheses of aging, suggests that certain cellular activities may be of physiologic benefit in youth but may untowardly decrease organismal fitness in later life. 1 The cancer-aging hypothesis represents a special case of this model, suggesting that tumor suppressor mechanisms such as cellular senescence can function in an antagonistically pleiotropic manner, ie, preventing malignant transformation in young mammals but promoting aging over a lifespan. Although there are examples of senescence-promoting tumor suppressor proteins such as p16 INK4a and p53 contributing to the aging of distinct tissue compartments (reviewed in Campisi 2 and Collado et al 3 ), it has not been possible to directly demonstrate a strict trade-off between increased aging and reduced cancer as the result of a cellautonomous activation of a specific tumor suppressor mechanism within an isolated tissue.The p16 INK4a tumor suppressor, along with 2 other tumor suppressor proteins, p15INK4b and p14 ARF (hereafter referred to solely as ARF), originates from the INK4/ARF or CDKN2a/b locus at human chromosome 9p21 (reviewed in Sharpless and DePinho 4 ). Expression of p16 INK4a inhibits the cell cycle, promotes cellular senescence, and has been linked to cancer and aging in mammalian systems. Expression of p16 INK4a has been shown to markedly increase with age in nearly all mammalian tissues, and caloric restriction, which retards aging in rodents, attenuates this age-induced increase in p16 INK4a . 19,20 because germline p16 INK4a -deficient mice have increased thymocyte and peripheral T-cell numbers. 21,22 Of particular importance to the present work, we and others have shown an accumulation of p16 INK4a expressing T cells in human peripheral blood with aging. 17,23 This expression of p16 INK4a appears to be a biomarker of physiologic as opposed to chronologic age, independently correlating with gerontogenic behaviors such as smoking and physical inactivity. 17 Although these murine and human data Submitted September 2, 2010; accepted December 9, 2010. Prepublished online as Blood First Edition paper, January 18, 2011; DOI 10.1182 DOI 10. /blood-2010 An Inside Blood analysis of this article appears at the front of this issue.The online version of this article contains a data supplement.The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked ''advertisement'' in accordance with 18 USC section 1734. With regard to lymphoid cancers, deletion and silencing of the INK4a/ARF locus are among the most common genetic events in a variety of human lymphoid and plasma cell malignancies, particularly pediatric B-and T-lineage acute lymphoblasti...

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Section: Attenuation Of Immune Aging Phenotypes After Deletion Of P16supporting

confidence: 79%

Expression of p16INK4a prevents cancer and promotes aging in lymphocytes

Liu¹,

Johnson²,

Fedoriw

et al. 2011

Blood

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“…This switching seemed more or less irreversible. The proportion of CD4+CD45RO+ cells in the peripheral blood increased with age [19], while the proportion of CD4+CD45RAf cells showed a gradual decline with age [14,20,21].Thus, CD45RA and CD45RO seemed to mark virgin and memory cells, respectively, in CD4+ T cells. Also in mice, it was reported that aged donors had lower proportion of CD45RBb@ cells in CD4+ Tcells [22].…”

Section: Introductionmentioning

confidence: 94%

Age‐related accumulation of LFA‐1^high cells in a CD8⁺CD45RA^high T cell population

et al. 1993

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The differential expression of CD45 isoforms has been suggested as a marker for stages of post-thymic T cell development, that is, CD45RA+CD45R0-T cells and CD45RA-CD45R0+ T cells are supposed to be virgin and memory cells respectively. Recently, several adhesion molecules have been shown to be up-regulated on the cell surface of memory T cells, and have been suggested to serve as a memory marker. In this study, we investigated the levels of LFA-1 expression on T cells in various subpopulations defined by CD45 isoform expression in donors of various ages. In CD4+ T cells, the proportion of LFA-1high cells among CD45RAhighCD45R0- T cells remained low in all age groups and did not show significant accumulation with age. CD4+CD45RA-CD45R0high T cells expressed LFA-1 at a higher level than CD4+CD45RAhighCD45R0- T cells. Thus, the currently prevailing view that CD45RA and CD45R0 can be markers for virgin and primed cells was consistent with LFA-1 expression in CD4+ T cell population. In CD8+ T cells, however, CD45RAhighCD45R0- T cells consisted of two distinct subpopulations, LFA-1low and LFA-1high cells, whereas CD45RA-CD45R0high T cells were almost exclusively LFA-1high. When CD29 expression was examined in place of LFA-1 expression, similar results were obtained; CD45RAhigh CD45R0- T cells consisted of two distinct subpopulations, CD29-to low and CD29high cells, while CD45RA-CD45R0high T cells were mostly CD29high. The proportion of LFA-1high cells in the CD8+CD45RAhigh T cell subpopulation increased significantly as a function of age (r = 0.9, p < 0.001). It ranged from 8% in a 14-year-old donor to 94% in a 79-year-old donor. Furthermore, the proportion of CD8+CD45RAhighLFA-1high cells in the CD8+ T cell population increased significantly as a function of age (r = 0.85, p < 0.001). On the other hand the proportion of LFA-1high cells in CD8+CD45RA- T cell subpopulation exceeded 90% in most donors irrespective of age. These results indicate that the CD8+CD45RAhighCD45R0- T cell subpopulation contains a considerable number of LFA-1high cells and CD29high cells, phenotypically similar to previously activated cells. Thus, in terms of LFA-1 and CD29 expressions, the simple scheme that CD45RA is a marker of virgin cells is not applicable to the CD8+ T cell population.

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“…The relative proportion of the two CD4+ T cell subsets changes with age. In cord blood (20) and among PBL of infants, the proportion of CD29+ CD4+ cells is low, whereas that of the CD45RA+ CD4+ subset is high (15). In vitro activation by various mitogens can result in a transition of naive T cells to primed or memory T cells with a concomitant switch of their cell surface antigenic profile (20).…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to acute gastroenteritis from other causes, G. lamblia-associated diarrhea did not elicit changes in lymphocyte subsets. (Pediatr Res 33: [15][16][17][18]1993) Abbreviations NK, natural killer PBL, peripheral blood lymphocyte PE, phycoerythrin however, yielded inconclusive results. Whereas in some studies of acute giardiasis an anti-Giardia IgM response was noted (5,6), in others, an increase in specific IgA but not IgM or IgG antibodies was observed (7).…”

mentioning

confidence: 99%