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mTOR signaling promotes a robust and continuous production of IFN-γ by human memory CD8+ T cells and their proliferation.

Abstract：

:Human CD8(+) T cells are functionally heterogeneous and can be divided into phenotypically and functionally distinct subsets according to CCR7 and CD45RA expression levels. Among these, CCR7(low) CD45RA(low) effector memory CD8(+) T cells (Tem) and CCR7(low) CD45RA(high) CD8(+) T cells, which are designated as Temra and considered to be terminally differentiated cells, are Ag-experienced T cells but show different functionalities. Here, we show that, while Tem proliferate vigorously and produce IFN-γ persistently and robustly, Temra proliferate poorly and lose the ability to produce IFN-γ over time after TCR stimulation. Temra showed impaired cell growth upon TCR stimulation, which was associated with defective activation of the mammalian target of rapamycin (mTOR) signaling. Furthermore, rapamycin, an inhibitor of mTOR signaling, interfered with the robust and continuous proliferation of and IFN-γ production by Tem at later time points after TCR stimulation. Thus, these data collectively indicate that activation of mTOR signaling is required for the robust functions of Tem cells in humans and suggest that defective mTOR signaling in Temra contributes to their functional impairment.

journal_name

Eur J Immunol

journal_title

European journal of immunology

authors

Setoguchi R,Matsui Y,Mouri K

doi

10.1002/eji.201445086

subject

Has Abstract

pub_date

2015-03-01 00:00:00

pages

893-902

issue

3

eissn

0014-2980

issn

1521-4141

journal_volume

45

pub_type

临床试验,杂志文章

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