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Hum Vaccin Immunother. 2014 May; 10(5): 1404–1405.
Published online 2014 January 8. doi:  10.4161/hv.27665
PMCID: PMC4896605

An age-related decline of CD62L and vaccine response

A role of microRNA 92a?

Abstract

Aging process can affect T cell and antibody response to vaccination and an age-related decline in the expression of CD62L on CD8+ T-lymphocyte is one of the important factors that contribute. A recent report demonstrated that percentage of CD3+CD8+CD62L+ cells and CD8+ T-lymphocyte microRNA-92a levels significantly decline with the age and were positively correlated. These results suggested that the age-related attrition of human naïve T cells could be connected to a reduced microRNA-92a in T-lymphocytes and downregulation of the microRNA-92a level might indicate exhaustion of naïve T-cells due to alteration of the immunologic condition with aging. Further studies are necessary to evaluate whether targeting microRNA-92a as microRNA mimics could be one of the therapeutic strategies in improving vaccine response in elderly.

Keywords: CD62L, CD8+ T-lymphocyte, immunosenescence, microRNA 92a, vaccine response

To the Editor

We read with interest the article by Rosenberg et al.1 They reported that the formation of antibodies in response to vaccination against hepatitis B virus was significantly reduced in elder donors (mean age of 61 y) compared with younger donors (mean age of 33 y), which might be due to different expression of the adhesion molecule CD62L (L-selectin) on naïve and central memory T cells between the 2 age groups.1 They described that their findings were consistent with the previous observation, showing CD62L gene ablation in animals altered the formation of antigen-specific antibodies and hypothesized that aging could have a possible functional impact on CD60L.1

However, we would like to add that age-related decline in the expression of CD62L regulated by microRNA-92a might also be important in immunosenescence-associated vaccine response. MicroRNAs consist of short noncoding RNA molecules of approximately 18–22 nucleotides, which regulate gene expression post-transcriptionally by repression or degradation of mRNA molecules and microRNA-17–92a cluster is known to regulate various aspects of immune system and is critical for lymphoid cellular development.2,3 Ohyashiki et al., recently reported that a significant decrease in the percentage of CD3+CD8+CD62L+ fraction was evident with the age. They further show that CD8+ T-lymphocyte microRNA-92a level was significantly decreased with age, whereas CD4+ lymphocytes only showed a tendency for a decrease in microRNA-92a level with age.4 They also demonstrated that there was a significant positive correlation between CD8+ microRNA-92a levels and the percentage of CD3+CD8+CD62L+ fraction, which tends to downregulate with age.4 They suggested that the age-related attrition of naïve T cells might be linked to a reduction in the levels of microRNA-92a in human T-lymphocytes and downregulation of the microRNA-92a level might indicate exhaustion of naïve T-cells due to alteration of the immunologic condition with aging, especially in individuals older than 60 y.4

Therefore, there is a possibility that the expression of CD62L on CD8+ T-lymphocyte could be affected by aging process, and microRNA-92a might have an important role in this process. Further studies are necessary to evaluate whether targeting microRNA-92a as microRNA mimics5 could be one of the therapeutic strategies in improving vaccine response in elderly population.

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

References

1. Rosenberg C, Bovin NV, Bram LV, Flyvbjerg E, Erlandsen M, Vorup-Jensen T, Petersen E. Age is an important determinant in humoral and T cell responses to immunization with hepatitis B surface antigen. Hum Vaccin Immunother 2013; 9:1466 - 76; http://dx.doi.org/; PMID: 23571167 10.4161/hv.24480 [PubMed] [Cross Ref]
2. He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 2004; 5:522 - 31; http://dx.doi.org/; PMID: 15211354 10.1038/nrg1379 [PubMed] [Cross Ref]
3. Xiao C, Srinivasan L, Calado DP, Patterson HC, Zhang B, Wang J, Henderson JM, Kutok JL, Rajewsky K. Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes. Nat Immunol 2008; 9:405 - 14; http://dx.doi.org/; PMID: 18327259 10.1038/ni1575 [PMC free article] [PubMed] [Cross Ref]
4. Ohyashiki M, Ohyashiki JH, Hirota A, Kobayashi C, Ohyashiki K. Age-related decrease of miRNA-92a levels in human CD8+ T-cells correlates with a reduction of naïve T lymphocytes. Immun Ageing 2011; 8:11; http://dx.doi.org/; PMID: 22082184 10.1186/1742-4933-8-11 [PMC free article] [PubMed] [Cross Ref]
5. Ling H, Fabbri M, Calin GA. MicroRNAs and other non-coding RNAs as targets for anticancer drug development. Nat Rev Drug Discov 2013; 12:847 - 65; http://dx.doi.org/; PMID: 24172333 10.1038/nrd4140 [PMC free article] [PubMed] [Cross Ref]

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