@article {541976,
	title = {Defective TFH Cell Function and Increased TFR Cells Contribute to Defective Antibody Production in Aging.},
	journal = {Cell Rep},
	volume = {12},
	number = {2},
	year = {2015},
	month = {2015 Jul 14},
	pages = {163-71},
	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.},
	issn = {2211-1247},
	doi = {10.1016/j.celrep.2015.06.015},
	author = {Sage, Peter T and Tan, Catherine L and Freeman, Gordon J and Haigis, Marcia and Sharpe, Arlene H}
}
