title: CD40L expression by CD4+but not CD8+T cells regulates antiviral immune responses in acute LCMV infection in mice.
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.
authors: Regenerative Immunology and Aging, Berlin-Brandenburger Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Berlin, Germany.|Cellular Biology, German Rheumatism Research Center (DRFZ), Institute of the Leibniz Association, Berlin, Germany.
authors: Sibel
authors: S
authors: Durlanik
authors: Regenerative Immunology and Aging, Berlin-Brandenburger Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Berlin, Germany.
authors: Lucie
authors: L
authors: Loyal
authors: Regenerative Immunology and Aging, Berlin-Brandenburger Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Berlin, Germany.|Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam, the Netherlands.
authors: Regina
authors: R
authors: Stark
authors: Cellular Biology, German Rheumatism Research Center (DRFZ), Institute of the Leibniz Association, Berlin, Germany.
authors: Özen
authors: Ö
authors: Sercan Alp
authors: Regenerative Immunology and Aging, Berlin-Brandenburger Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Berlin, Germany.
authors: Anett
authors: A
authors: Hartung
authors: Cellular Biology, German Rheumatism Research Center (DRFZ), Institute of the Leibniz Association, Berlin, Germany.
authors: Andreas
authors: A
authors: Radbruch
authors: Type 1 Diabetes Center, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.|Novo Nordisk Diabetes Research and Development Center, Seattle, WA, USA.
authors: Matthias
authors: M
authors: von Herrath
authors: Regenerative Immunology and Aging, Berlin-Brandenburger Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Berlin, Germany.|Unit 303, Efficacy and Safety Assessment of Veterinary Drugs, Federal Office of Consumer Protection and Food Safety (BVL), Berlin, Germany.
authors: Nadine
authors: N
authors: Matzmohr
authors: Regenerative Immunology and Aging, Berlin-Brandenburger Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Berlin, Germany.
authors: Marco
authors: M
authors: Frentsch
authors: Regenerative Immunology and Aging, Berlin-Brandenburger Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Berlin, Germany. andreas.thiel@charite.de.
authors: Andreas
authors: A
authors: Thiel
mesh_terms: D000208:Acute Disease; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000235:genetics / Q000276:immunology; D023201:CD40 Ligand / Q000172:deficiency / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D005786:Gene Expression Regulation; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D019013:CD40 Antigens; D016207:Cytokines; D023201:CD40 Ligand
keywords: Antiviral T-cell responses; CD40 ligand; CD8+ T cells; LCMV; Viral clearance