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

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.

Usefulness of chemokine C‐C receptor 7−/programmed cell death‐1+ follicular helper T cell subset frequencies in the diagnosis of autoimmune hepatitis

“…Second, the number of patients in the various groups was not equal, and we could not control the background. Nevertheless, a study showed no significant difference between younger subjects and older subjects . In addition, the lack of patients with AIH and DILI might have affected the results of this study.…”

Defective TFH Cell Function and Increased TFR Cells Contribute to Defective Antibody Production in Aging

“…The slight increase in T fh cells in blood of aged mice is likely due to memory cells, since we have shown that blood T fh and T fr cells have characteristics of memory cells (Sage et al, 2014a). Blood T fh cells in aged humans express the memory marker CD45RO (Zhou et al, 2014). T fr cells, defined as CD4 + ICOS + CXCR5 + FoxP3 + CD19 − cells, were similarly low in percentage in the iLN and blood of unimmunized young and aged mice (Figure 1C).…”

“…A previous study found no difference in CXCR5 + cells in aged mice; however, T fr cells were not examined (Eaton et al, 2004). A recent study found slight increases in T fh cells in the blood of aged human subjects, but T fr cells were not evaluated (Zhou et al, 2014). Understanding changes in T fh and T fr cells during aging is important because both of these cell types directly interact with cognate B cells and control antibody production.…”

Increasing incidence of elderly‐onset autoimmune hepatitis

“…When aged B cells are exposed to self‐antigens, they can be accidentally activated and can produce low‐affinity, self‐reactive antibodies . Age‐associated increase in the circulating levels of pro‐inflammatory mediators, such as tumor necrosis factor‐α, interleukin‐6 and CRP, may recruit inflammatory cells and contribute to autoimmunity . Interferon‐α production in healthy Japanese individuals was reported to decline during mid‐50s or early 60s and then recover as they aged over 65 years, generating a concave U‐shaped pattern .…”