The effect of ageing on human lymphocyte subsets: comparison of males and females

Yan, Jun; Greer, Judith M.; Hull, Renee; O’Sullivan, John D.; Henderson, Robert D.; Read, Stephen; McCombe, Pamela A.

doi:10.1186/1742-4933-7-4

Cited by 141 publications

(125 citation statements)

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“…With respect to T-cells, however, although some studies have reported changes in T cell levels, especially a decrease in the CD8 cells with increasing age [2,10,11,[32][33][34], other (older) have reported increase in CD4+ and /or CD8+ [24,35,36]. The impact of age on lymphocyte subsets is not well established, with contradictory results from various studies.…”

Section: A U T H O R P R O O F Future Science Groupmentioning

confidence: 80%

Reference Ranges of Lymphocyte Subsets in Healthy Qatari Adults

Althani¹,

Hamdi²,

Al-Marwani³

et al. 2014

Biomark. Med.

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Aim: Determine reference ranges of lymphocyte subsets in healthy Qatari adults. Patients & Methods: Blood samples (n = 150) were investigated using four colors flow cytometery. Results: The mean percentage and absolute values of the lymphocyte subsets were: CD3: 73.6 ± 6.1%; 2,072 ± 644 cells/μl; CD4: 41.1 ± 7.9%; 1,167 ± 396 cells/ μl; CD8: 33.8 ± 7.1%; 967 ± 364 cells/μl; B cells (CD19+): 11.3 ± 3.9%; 318 ± 144 cells/μl and natural killer (NK) cells (CD16/56+): 16.5 ± 6.3%, 440 ± 401 cells/μl, respectively. The CD4/CD8 ratio was 1.3 ± 0.5. The ratio, CD3+ and CD4+ percentage and CD4+ cell counts were significantly higher in females; CD8+ and NK cell count and CD8+ percentage were significantly higher in males. The impact of age was less certain. Conclusion:The reference values of lymphocyte subsets appear to be specific to this population, demonstrating the importance of establishing local reference ranges. Keywords: B cells • CD3 • CD4 • CD8 • flow cytometry • lymphocyte subsets • natural killer cells • reference ranges, IntroductionLymphocyte immunophenotyping by flow cytometry is an important tool in differential diagnosis of congenital and acquired immune deficiencies, lymphoproliferative disorders and acute leukemias [1]. In addition, it is used for monitoring treatment response and disease progression with anti-retroviral and immunosuppressive therapy. Various studies suggest that lymphocyte subsets reference ranges are influenced by age, sex, ethnicity, and environment [2][3][4][5]. The variations in the values of the lymphocyte subsets emphasize the importance of establishing local reference ranges to allow for meaningful comparisons and accurate interpretation of immunophenotyping data across different cultures and ethnic groups. Lifestyle factors, e.g. smoking, have also been shown to influence lymphocyte subset values [6,7].Indeed, reference range for peripheral blood lymphocyte subsets have been established in many studies across different countries, revealing variations in the normal range for lymphocyte subsets according to age, sex, race, and environmental factors [3,4,[8][9][10][11][12][13][14][15][16]. Establishment of an internal normal range of lymphocyte subsets is a important for each population considering the effect of environmental factors, age, ethnical diversity on the immune system. Hence, this study aims to determine the laboratory reference ranges for lymphocyte subsets in healthy Qatari adults using flow cytometry.This article reports the local reference range for peripheral blood lymphocyte subsets, both percentages and absolute counts, in a representative sample of 150 healthy adult Qatari population.The results have been stratified by age, sex, and smoking status. The population selected is largely homogenous (100% Qatari Arabs) so effect of race was not investigated. The results are briefly compared with other population data from published studies. Materials & methods SubjectsA total of 150 healthy Qatari volunteers (18-55 yr old; all Qatari Arabs) were recruited for the stud...

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Section: A U T H O R P R O O F Future Science Groupmentioning

confidence: 80%

Reference Ranges of Lymphocyte Subsets in Healthy Qatari Adults

Althani¹,

Hamdi²,

Al-Marwani³

et al. 2014

Biomark. Med.

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“…Other authors have described a significant decrease of CD8 + T cells with no significant changes in CD4 + T cells with ageing, leading to an unexpected increase in the CD4:CD8 ratio (Gruver et al, 2007;Yan et al, 2010).…”

Section: Inflamm-ageing and T Lymphocytesmentioning

confidence: 99%

B cells and immunosenescence: A focus on IgG+IgD−CD27− (DN) B cells in aged humans

Bulati¹,

Buffa²,

Candore³

et al. 2011

Ageing Research Reviews

101

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a b s t r a c tImmunosenescence contributes to the decreased ability of the elderly to control infectious diseases, which is also reflected in their generally poor response to new antigens and vaccination. It is known that the T cell branch of the immune system is impaired in the elderly mainly due to expansion of memory/effector cells that renders the immune system less able to respond to new antigens. B lymphocytes are also impaired in the elderly in terms of their response to new antigens. In this paper we review recent work on B cell immunosenescence focusing our attention on memory B cells and a subset of memory B cells (namely IgG + IgD − CD27 − ) that we have demonstrated is increased in healthy elderly.

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“…A study performed by Yan and colleagues indicated that in both males and females, aging leads to a significant decline in the percentage of naive CD4 + and CD8 + T cells and an increase in the percentage of memory T cells, FOXP3 + Tregs , and NK cells (119). However, their data also suggest that the decline in CD8 + T cell frequency and the corresponding increase in the percentage of memory T cells occurs significantly faster in male than in female subjects (119). Another recent study performed on ethnically Japanese populations of males and females of different ages reported similar age-related changes in immune cell populations.…”

Section: Sex-dependent Changes In the Aging Immune Systemmentioning

confidence: 99%

Sexual dimorphism in autoimmunity

Rubtsova¹,

Marrack²,

Rubtsov³

2015

J. Clin. Invest.

175

127

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R e v i e w S e R i e S : A u t o i m m u n i t y 2 1 8 8jci.org Volume 125 Number 6 June 2015expression of IFN1 genes is controlled directly by sex hormones. On the other hand, sex hormones do affect expression of some of the PRRs (see below) and in this way might indirectly affect IFN1 levels. Thus, the abundance of IFN1s in lupus patients might be caused by female sex hormone-induced increases in PRR levels, which in turn increase production of IFN1s. One of the genes that controls expression of IFN1s is IFN regulatory factor 5 (IRF5). IRF5 has also been identified as a significant risk factor for lupus susceptibility (37,38). Expression of IRF5 in mice has been reported to be sex dependent (39). As demonstrated by Shen and colleagues (39), C57BL/6, NZB, Nba2, NZB/NZW F1, and NZM mouse strains express significantly higher levels of Irf5 mRNA in female than in male lymphocytes. Additionally, splenocytes from lupus-prone mice were shown to express higher levels of Irf5 mRNA compared with cells from the C57BL/6 strain, which is not prone to lupus. This group further demonstrated that Irf5 expression can be upregulated in vitro upon estrogen treatment, suggesting a potential mechanism for sex-biased expression of the gene and consequent overproduction of IFN1s (39).Absence of IFN-γ signaling protects NZB/NZW F1 mice against lupus-like disease (40). Expression of the IFNG gene, on the other hand, is regulated directly by estrogens (41)(42)(43)(44)(45). This finding suggests a positive feedback loop between the IFNs and estrogens, since activation of IFN1 or IFN-γ signaling upregulates the expression of ERα (46). Estrogen, in turn, promotes IFN-γ production by various lymphocytes. In addition, Panchanathan et al. demonstrated synergistic involvement of ERα and IFN signaling in activating the transcription of both IFN and estrogen-responsive target genes (46).Once produced, IFNs have many effects on the immune system that contribute to the sex bias of autoimmunity. For example, IFN1s increase class 1 MHC expression on cells, and IFN-γ induces class II MHC and changes the nature of the proteasome, thereby affecting the nature and quantity of self-peptides presented to T cells. Other examples are described below. Other immune-associated genes affected by sex hormonesMany genes with products that affect the immune system are controlled by sex hormones. As far as innate immunity is concerned, estrogens induce the expression of intracellular but not surface TLRs in both male and female PBMCs (23). Because intracellular TLRs have been shown to affect the development of autoimmunity (47-51), it is possible that the hormonal effect of the expression of intracellular TLRs contributes to female-biased autoimmunity.Unc-93 homolog B1 (UNC93B1) is an endoplasmic reticulum (ER) transmembrane protein that is essential for trafficking the TLRs that are expressed intracellularly (TLR3, TLR7, TLR8, TLR9, and probably other TLRs) from the ER to endosomes (52-54). UNC93B1 regulates the activity of these TLRs by mediating localization t...

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The effect of ageing on human lymphocyte subsets: comparison of males and females

Cited by 141 publications

References 68 publications

Reference Ranges of Lymphocyte Subsets in Healthy Qatari Adults

Reference Ranges of Lymphocyte Subsets in Healthy Qatari Adults

B cells and immunosenescence: A focus on IgG+IgD−CD27− (DN) B cells in aged humans

Sexual dimorphism in autoimmunity

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