Age-associated changes within CD4+ T cells

Kovaiou, Rania D.; Grubeck‐Loebenstein, Beatrix

doi:10.1016/j.imlet.2006.07.006

Cited by 71 publications

(54 citation statements)

References 80 publications

(92 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although some studies suggest that the age-associated defects in CD8 + T cell responses relate to impaired Ag-presentation (48,49), hypofunctionality of CD4 + T cells (50,51) or loss of naive T cells after thymic involution (40,52) and a decline in the proliferative capacity of hematopoietic stem cells (53), other studies suggest an intrinsic defect in aged CD8 + T cells (54) potentially by cell senescence and its associated changes in the cells' genome and epigenome. Immunoinhibitory pathways may become more predominant on aging.…”

Section: Discussionmentioning

confidence: 99%

Augmentation of Primary Influenza A Virus-Specific CD8+ T Cell Responses in Aged Mice through Blockade of an Immunoinhibitory Pathway

DiMenna

Latimer

Parzych

et al. 2010

The Journal of Immunology

View full text Add to dashboard Cite

Immune responses diminish with age resulting in an increased susceptibility of the elderly to infectious agents and an inability to mount protective immune responses to vaccines. Immunosenescence affects multiple aspects of the immune system, including CD8+ T cells, which control viral infections and are assumed to prevent the development of cancers. In this study, we tested if CD8+ T cell responses in aged mice could be enhanced through a vaccine that concomitantly expresses Ag and a molecule that blocks an immunoinhibitory pathway. Specifically, we tested a vaccine based on a replication-defective chimpanzee-derived adenovirus vector expressing the nucleoprotein (NP) of influenza A virus as a fusion protein with the HSV type 1 glycoprotein D, which through binding to the herpes virus entry mediator, blocks the immunoinhibitory herpes virus entry mediator B and T lymphocyte attenuator/CD160 pathways. Our results show that the vaccine expressing a fusion protein of NP and glycoprotein D induces significantly higher NP-specific CD8+ T cell responses in young and aged mice compared with the vaccine expressing NP only.

show abstract

Section: Discussionmentioning

confidence: 99%

Augmentation of Primary Influenza A Virus-Specific CD8+ T Cell Responses in Aged Mice through Blockade of an Immunoinhibitory Pathway

DiMenna

Latimer

Parzych

et al. 2010

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Indeed, there is experimental evidence showing that after the age of 65-70 years, an accurate phenotypic distinction amongst naïve and memory cells can not be made (Goronzy et al, 2007;Kovaiou and Grubeck-Loebenstein, 2006). The results of Goronzy et al, (2007) and others (Hakim et al, 2005) Separation of the PCA-extracted H1 fraction was accomplished by CZE and mixing experiments with recombinantly expressed H1 subtypes were used to determine the identity of the main peaks.…”

Section: Discussionmentioning

confidence: 99%

H1 histone subtype constitution and phosphorylation state of the ageing cell system of human peripheral blood lymphocytes

Happel

Doenecke

Sekeri‐Pataryas

et al. 2008

Experimental Gerontology

View full text Add to dashboard Cite

“…Although both EM and EMRA T cells have proliferative defects, the latter population can exhibit potent effector functions (5,7,9,10). Highly differentiated populations of EM and EMRA-like CD4 + and CD8 + T cells have been shown to accumulate in older human (7,(11)(12)(13) patients with persistent viral infections (14)(15)(16)(17)(18) and those with inflammatory syndromes such as rheumatoid arthritis (19)(20)(21). In addition, EMRA T cells are the dominant memory population that persists after some forms of vaccination (22).…”

Section: Cd27mentioning

confidence: 99%

Reversible Senescence in Human CD4+CD45RA+CD27− Memory T Cells

Mitri

Azevedo

Henson

et al. 2011

The Journal of Immunology

202

170

View full text Add to dashboard Cite

Persistent viral infections and inflammatory syndromes induce the accumulation of T cells with characteristics of terminal differentiation or senescence. However, the mechanism that regulates the end-stage differentiation of these cells is unclear. Human CD4+ effector memory (EM) T cells (CD27−CD45RA−) and also EM T cells that re-express CD45RA (CD27−CD45RA+; EMRA) have many characteristics of end-stage differentiation. These include the expression of surface KLRG1 and CD57, reduced replicative capacity, decreased survival, and high expression of nuclear γH2AX after TCR activation. A paradoxical observation was that although CD4+ EMRA T cells exhibit defective telomerase activity after activation, they have significantly longer telomeres than central memory (CM)-like (CD27+CD45RA−) and EM (CD27−CD45RA−) CD4+ T cells. This suggested that telomerase activity was actively inhibited in this population. Because proinflammatory cytokines such as TNF-α inhibited telomerase activity in T cells via a p38 MAPK pathway, we investigated the involvement of p38 signaling in CD4+ EMRA T cells. We found that the expression of both total and phosphorylated p38 was highest in the EM and EMRA compared with that of other CD4+ T cell subsets. Furthermore, the inhibition of p38 signaling, especially in CD4+ EMRA T cells, significantly enhanced their telomerase activity and survival after TCR activation. Thus, activation of the p38 MAPK pathway is directly involved in certain senescence characteristics of highly differentiated CD4+ T cells. In particular, CD4+ EMRA T cells have features of telomere-independent senescence that are regulated by active cell signaling pathways that are reversible.

show abstract

Age-associated changes within CD4+ T cells

Cited by 71 publications

References 80 publications

Augmentation of Primary Influenza A Virus-Specific CD8+ T Cell Responses in Aged Mice through Blockade of an Immunoinhibitory Pathway

Augmentation of Primary Influenza A Virus-Specific CD8+ T Cell Responses in Aged Mice through Blockade of an Immunoinhibitory Pathway

H1 histone subtype constitution and phosphorylation state of the ageing cell system of human peripheral blood lymphocytes

Reversible Senescence in Human CD4+CD45RA+CD27− Memory T Cells

Contact Info

Product

Resources

About