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Eur J Immunol. 2016 Nov;46(11):2566-2573. doi: 10.1002/eji.201646420. Epub 2016 Sep 20.

CD40L expression by CD4+ but not CD8+ T cells regulates antiviral immune responses in acute LCMV infection in mice.

Author information

1
Regenerative Immunology and Aging, Berlin-Brandenburger Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Berlin, Germany.
2
Cellular Biology, German Rheumatism Research Center (DRFZ), Institute of the Leibniz Association, Berlin, Germany.
3
Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam, the Netherlands.
4
Type 1 Diabetes Center, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
5
Novo Nordisk Diabetes Research and Development Center, Seattle, WA, USA.
6
Unit 303, Efficacy and Safety Assessment of Veterinary Drugs, Federal Office of Consumer Protection and Food Safety (BVL), Berlin, Germany.
7
Regenerative Immunology and Aging, Berlin-Brandenburger Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Berlin, Germany. andreas.thiel@charite.de.

Abstract

CD40-CD40 ligand (CD40L) signaling plays multiple indispensable roles in cellular and humoral immunity. Impaired memory T-cell responses in the absence of CD40L have been well documented, but the requirement of this interaction for efficient priming of CD8+ T cells especially under inflammatory conditions has been under debate. In contrast to previous publications, we report here that virus-specific CD8+ T-cell responses as well as viral clearance are affected not only in the memory but also in the effector phase in CD40L-/- mice infected with lymphocytic choriomeningitis virus (LCMV) Armstrong strain. Interestingly, a considerable part of the LCMV-specific effector and memory T cells consists of CD40L+ CD8+ T cells. However, deficiency of CD40L in CD8+ T cells did influence neither the quantity nor the quality of primary T-cell responses in LCMV infection. Virus-specific CD8+ T cells in conditional knockout mice, with a selective deletion of the CD40L in CD8+ T cells, were fully functional regarding cytokine production and efficient pathogen clearance. Thus, our results unambiguously demonstrate that while CD40L is critical to generate effective primary CD8+ T-cell responses also under inflammatory conditions, CD40L expression by CD8+ T cells themselves is dispensable in acute LCMV infection.

KEYWORDS:

Antiviral T-cell responses; CD40 ligand; CD8+ T cells; LCMV; Viral clearance

PMID:
27562840
DOI:
10.1002/eji.201646420
[Indexed for MEDLINE]
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