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. 2004 May 15;172(10):6107-14.
doi: 10.4049/jimmunol.172.10.6107.

The size and phenotype of virus-specific T cell populations is determined by repetitive antigenic stimulation and environmental cytokines

Laila E Gamadia  1 , Ester M M van Leeuwen, Ester B M Remmerswaal, Si-La Yong, Sugianto Surachno, Pauline M E Wertheim-van Dillen, Ineke J M Ten Berge, René A W Van Lier
Affiliations

The size and phenotype of virus-specific T cell populations is determined by repetitive antigenic stimulation and environmental cytokines

Laila E Gamadia et al. J Immunol. .

Abstract

Based on the expression of the TNFR SFP CD27, two Ag-primed CD8(+) T cell subsets can be discerned in the circulation of healthy individuals: CD27(+) T cells that produce a variety of cytokines but do not display immediate cytolytic activity; and cytotoxic CD27(-) T cells, which secrete only IFN-gamma and TNF-alpha. The mechanism that controls the generation of these different phenotypes is unknown. We show that CMV reactivation not only increases the number of virus-specific T cells but also induces their transition from a CD27(+) to a CD27(-) phenotype. In support of a relation between pool size and phenotype in a cohort of latently infected individuals, the number of Ag-specific CD27(-) CD8(+) T cells was found to be linearly related to the total number of CMV-specific CD8(+) T cells. In vitro studies revealed that the acquisition of the CD27(-) phenotype on CMV-specific T cells depended on the interaction of CD27 with its cellular ligand, CD70. Expression of CD70 was proportional to the amount of antigenic stimulation and blocked by the CD4(+) T cell-derived cytokine IL-21. Thus, induction of CD70, which may vary in distinct viral infections, appears to be a key factor in determining the size and phenotype of the CMV-specific T cell population in latently infected individuals.

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