The size and phenotype of virus-specific T cell populations is determined by repetitive antigenic stimulation and environmental cytokines |
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Authors: | Gamadia Laila E van Leeuwen Ester M M Remmerswaal Ester B M Yong Si-La Surachno Sugianto Wertheim-van Dillen Pauline M E Ten Berge Ineke J M Van Lier René A W |
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Institution: | Renal Transplant Unit, Department of Internal Medicine, Laboratory for Experimental Immunology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. |
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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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