Acquisition of direct antiviral effector functions by CMV-specific CD4+T lymphocytes with cellular maturation

Casazza, Joseph P., Betts, Michael R., Price, David ORCID: https://orcid.org/0000-0001-9416-2737, Precopio, Melissa L., Ruff, Laura E., Brenchley, Jason M., Hill, Brenna J., Roederer, Mario, Douek, Daniel C. and Koup, Richard A. 2006. Acquisition of direct antiviral effector functions by CMV-specific CD4+T lymphocytes with cellular maturation. Journal of Experimental Medicine 203 (13) , pp. 2865-2877. 10.1084/jem.20052246

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Abstract

The role of CD4+ T cells in the control of persistent viral infections beyond the provision of cognate help remains unclear. We used polychromatic flow cytometry to evaluate the production of the cytokines interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-2, the chemokine macrophage inflammatory protein (MIP)-1β, and surface mobilization of the degranulation marker CD107a by CD4+ T cells in response to stimulation with cytomegalovirus (CMV)-specific major histocompatibility complex class II peptide epitopes. Surface expression of CD45RO, CD27, and CD57 on responding cells was used to classify CD4+ T cell maturation. The functional profile of virus-specific CD4+ T cells in chronic CMV infection was unique compared with that observed in other viral infections. Salient features of this profile were: (a) the simultaneous production of MIP-1β, TNF-α, and IFN-γ in the absence of IL-2; and (b) direct cytolytic activity associated with surface mobilization of CD107a and intracellular expression of perforin and granzymes. This polyfunctional profile was associated with a terminally differentiated phenotype that was not characterized by a distinct clonotypic composition. Thus, mature CMV-specific CD4+ T cells exhibit distinct functional properties reminiscent of antiviral CD8+ T lymphocytes.

Item Type:	Article
Status:	Published
Schools:	Medicine
Publisher:	Rockefeller University Press
ISSN:	0022-1007
Date of First Compliant Deposit:	29 April 2016
Last Modified:	04 May 2023 14:24
URI:	https://orca.cardiff.ac.uk/id/eprint/90181

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