title: IL-4 directs both CD4 and CD8 T cells to produce Th2 cytokines in vitro, but only CD4 T cells produce these cytokines in response to alum-precipitated protein in vivo.
abstract: While IL-4 directs CD4 T cells to produce Th2 cytokines (including IL-4, IL-13, IL-5) in vitro it has been shown that production of these cytokines can be induced in vivo in the absence of IL-4/IL-13/STAT-6 signaling. The present report shows that CD8 as well as CD4 T cells activated through their TCR, in vitro upregulate the Th2-features - IL-4, IL-13, IL-5, and GATA-3. However, in vivo while alum-precipitated antigen strongly and selectively induces these Th2-features in CD4 T cells, CD8 T cells mount a markedly different response to this antigen. This CD8 response is associated with strong proliferation and production of IFN-gamma, but no Th2-features are induced. Alum-protein formulations are widely used in human vaccines and typically induce strong antibody responses characterized by the differentiation of IL-4-producing CD4 T cells and immunoglobulin class switching to IgG1. Nevertheless, the mechanism responsible for CD4 Th2 and follicular helper T cell commitment triggered by these alum-protein vaccines is still poorly understood. Analysis of the in vivo response to alum-precipitated protein shows that while subsets of CD4 T cells strongly upregulate Th2 and follicular helper T cell features including the surface markers OX40, CXCR5, PD-1, IL-17RB and the transcription factor c-Maf, CD8 T cells do not. These discrete differences between responding CD4 and CD8 T cells provide further insight into the differences between Th2 polarization of CD4 T cells directed by IL-4 in vitro and the induction of IL-4 production by CD4 T cells in vivo in response to alum-precipitated protein.
authors.affiliation: MRC Centre for Immune Regulation, the IBR, School of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, United Kingdom. karine@kserre.net <karine@kserre.net>
authors.forename: Karine
authors.initials: K
authors.lastname: Serre
authors.forename: Elodie
authors.initials: E
authors.lastname: Mohr
authors.forename: Fabrina
authors.initials: F
authors.lastname: Gaspal
authors.forename: Peter J L
authors.initials: PJ
authors.lastname: Lane
authors.forename: Roger
authors.initials: R
authors.lastname: Bird
authors.forename: Adam F
authors.initials: AF
authors.lastname: Cunningham
authors.forename: Ian C M
authors.initials: IC
authors.lastname: Maclennan
mesh_terms: D000534:Alum Compounds / Q000494:pharmacology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002469:Cell Separation; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D005434:Flow Cytometry; D007155:Immunologic Factors / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000534:Alum Compounds; D016207:Cytokines; D007155:Immunologic Factors; C110366:OVA-8; D010446:Peptide Fragments; D015847:Interleukin-4; D010047:Ovalbumin
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