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

ABSTRACT: Defective antibody production in aging is broadly attributed to immunosenescence. However, the precise immunological mechanisms remain unclear. Here, we demonstrate an increase in the ratio of inhibitory T follicular regulatory (TFR) cells to stimulatory T follicular helper (TFH) cells in aged mice. Aged TFH and TFR cells are phenotypically distinct from those in young mice, exhibiting increased programmed cell death protein-1 expression but decreased ICOS expression. Aged TFH cells exhibit defective antigen-specific responses, and programmed cell death protein-ligand 1 blockade can partially rescue TFH cell function. In contrast, young and aged TFR cells have similar suppressive capacity on a per-cell basis in vitro and in vivo. Together, these studies reveal mechanisms contributing to defective humoral immunity in aging: an increase in suppressive TFR cells combined with impaired function of aged TFH cells results in reduced T-cell-dependent antibody responses in aged mice.

SUBMITTER: Sage PT

PROVIDER: S-EPMC4504745 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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

Sage Peter T PT Tan Catherine L CL Freeman Gordon J GJ Haigis Marcia M Sharpe Arlene H AH

Cell reports 20150702 2

Defective antibody production in aging is broadly attributed to immunosenescence. However, the precise immunological mechanisms remain unclear. Here, we demonstrate an increase in the ratio of inhibitory T follicular regulatory (TFR) cells to stimulatory T follicular helper (TFH) cells in aged mice. Aged TFH and TFR cells are phenotypically distinct from those in young mice, exhibiting increased programmed cell death protein-1 expression but decreased ICOS expression. Aged TFH cells exhibit defe ...[more]

PMID: 26146074

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Project description:Background: Follicular helper T (Tfh) cells and follicular regulatory T (Tfr) cells are essential for B cell differentiation, germinal center formation, and humoral immune responses. Immunity and inflammation have been thought to be involved in Parkinson's disease (PD). In this study, we aimed to identify whether circulating Tfh and Tfr (cTfh and cTfr) cells contribute to PD. Methods: Thirty-nine PD patients and 26 health controls (HCs) were enrolled. The numbers of cTfh (CD4+CXCR5+PD-1+) cells and cTfr (CD4+CXCR5+CD25hiCD127low) cells were analyzed via flow cytometry. The serum concentrations of interleukin (IL)-4, IL-10, IL-21, and transforming growth factor (TGF)-β were examined by cytometric bead array. Results: The percentage of cTfh cells among CD4+ T cells in PD patients was significantly higher than that in HCs [3.68% (2.64-5.70%) vs. 1.94% (1.32%-2.99%), P < 0.001], while the percentage of cTfr cells among CD4+ T cells in PD patients was slight decreased but without significance [1.05% (0.62-1.54%) vs. 1.3% (0.63-1.90%), P > 0.05]. The percentage of CD19+ B cells in peripheral blood mononuclear cells was significantly lower in PD patients than in HCs [5.35% (4.13-9.38%) vs. 8.68% (5.61-12.93%), P = 0.014]. The serum concentrations of IL-4, IL-10, IL-21, and TGF-β in PD patients did not differ significantly from those in HCs (P > 0.05). There was a positive trend of the correlation between the number of cTfh and the serum IL-4 concentrations in PD patients (P = 0.032, r = 0.353). There was a positive trend of the correlation between the number of cTfr and the serum IL-10 concentrations in PD patients (P = 0.047, r = 0.328), A positive trend of the correlation were found for the serum concentration of IL-21 with H-Y stage (r = 0.356, P = 0.026) and UPDRS-III score (r = 0.347, P = 0.030). Conclusions: These results indicate that an imbalance of cTfh and cTfr cells may be involved in the chronic progression of PD, and IL-21 may be a biomarker for monitoring the severity of this disease.

Dataset Information

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

Publications

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

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