The effect of aging on the frequency, phenotype and cytokine production of human blood CD4 + CXCR5 + T follicular helper cells: comparison of aged and young subjects.

Maohua Zhou,Yanfei Luo,Fang He,Ruqiong Zou,Erxia Shen,Zhimei Liang,Xiaoming Cai,Fujun Li,Huiquan Gan,Ting Lin

doi:10.1186/1742-4933-11-12

Abstract

BackgroundT cell-dependent B-cell responses decline with age, indicating declined cognate helper activity of aged CD4 + T cells for B cells. However, the mechanisms remain unclear. T follicular helper (Tfh) cells, a novel T helper subset, play an essential role in helping B cells differentiation into long-lived plasma cells in germinal center (GC) or short-lived plasma cells. In the present study, we proposed that there might existe changes of proportion, phenotype or cytokine production of blood Tfh cells in healthy elderly individuals compared with healthy young individuals.ResultsThe results showed that frequencies of aged blood CXCR5 + CD4 + Tfh cells increased compared with young subjects. Both aged and young blood CXCR5 + CD4 + Tfh cells constitutively expressed CD45RO, CCR7 and CD28, and few of these cells expressed CD69 or HLA-DR, which indicated that they were resting memory cells. There was no significant difference of IL-21 frequency production by aged blood CXCR5 + CD4 + Tfh determined by FACS compared with young individuals, however, aged PBMCs produced significantly higher levels of IL-21 evaluated by ELISA. Furthermore, there were no significant differences of percentages of IFN-γ, IL-4, IL-17 or IL-22 production by aged Tfh cells compared with their counterparts of young individuals respectively. However, frequencies of IL-17+ cells within aged CD4 + CXCR5-T cells were markedly lower than in the young individuals. Furthermore we observed different frequencies of IFN-γ, IL-17, IL-4 or IL-22 production by Tfh or by CD4 + CXCR5- cells in aged and young subjects respectively.ConclusionsOur data demonstrated that the frequencies of blood memory CXCR5 + CD4 + Tfh cells increased in the elderly population. There were similar frequencies of Th characterized cytokine production such as IL-21, IFN-γ, IL-4, IL-17 or IL-22 in aged and young Tfh cells. However, aged PBMCs produced a significantly higher amount of IL-21 compare to young subjects.

Highlights

The immune system undergoes significant changes with aging, which likely partly contributes to increased susceptibility to infections, malignancies, inflammatory diseases, and reduced response to vaccination of elderly individuals [1,2]
There was no significant difference of cell counts of CXCR5 + CD4 + T follicular helper (Tfh) cells between aged and young subjects (Figure 1E)
These results demonstrated that aged blood CXCR5 + CD4 + Tfh cells proportion increased compared with young subjects

Summary

Introduction

The immune system undergoes significant changes with aging, which likely partly contributes to increased susceptibility to infections, malignancies, inflammatory diseases, and reduced response to vaccination of elderly individuals [1,2]. Significant decline in immune function during aging is termed immunosenescence [3], and higher frequencies of inflammatory diseases of elderly people indicate that aging could be regarded as a condition of dys-regulated inflammation [4]. Age-associated changes in NK cell phenotype have been previously reported that can be responsible of functional NK cell deficiency [5,6]. DCs from elderly individuals are compromised in response to microorganisms but display increased reactivity to self-antigens associated with chronic inflammation and autoimmunity [7,8,9]. We proposed that there might existe changes of proportion, phenotype or cytokine production of blood Tfh cells in healthy elderly individuals compared with healthy young individuals

Methods

Results

Discussion

Conclusion