CD28 Costimulation of T Helper 1 Cells Enhances Cytokine Release In Vivo

Compared to naive T cells, differentiated T cells are thought to be less dependent on CD28 costimulation for full activation. To revisit the role of CD28 costimulation in mouse T cell recall responses, we adoptively transferred generated OT-II T helper (Th) 1 cells into C57BL/6 mice (Thy1.2 ) and th...

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Bibliographic Details
Published in:	Frontiers in immunology Vol. 9; p. 1060
Main Authors:	Langenhorst, Daniela, Haack, Stephanie, Göb, Selina, Uri, Anna, Lühder, Fred, Vanhove, Bernard, Hünig, Thomas, Beyersdorf, Niklas
Format:	Journal Article
Language:	English
Published:	Switzerland Frontiers 16-05-2018 Frontiers Media S.A
Subjects:	Animals antigenic recall Biomarkers CD28 Antigens - immunology CD28 costimulation CD4+ T helper cells CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - metabolism Cell Differentiation - immunology cytokine secretion Cytokines - biosynthesis Cytokines - blood GATA3 Transcription Factor - genetics GATA3 Transcription Factor - metabolism Gene Expression Regulation Humans Immunologic Memory Immunology Immunophenotyping Leukocytes, Mononuclear - immunology Leukocytes, Mononuclear - metabolism Life Sciences Lymphocyte Activation - immunology Mice Mice, Transgenic mouse T helper 1 cells T-Box Domain Proteins - genetics Th1 Cells - immunology Th1 Cells - metabolism T helper 1 cells mouse cytokine secretion antigenic recall CD28 costimulation CD4+ T helper cells human cD4+ T helper cells cD28 costimulation
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Summary:	Compared to naive T cells, differentiated T cells are thought to be less dependent on CD28 costimulation for full activation. To revisit the role of CD28 costimulation in mouse T cell recall responses, we adoptively transferred generated OT-II T helper (Th) 1 cells into C57BL/6 mice (Thy1.2 ) and then either blocked CD28-ligand interactions with Fab fragments of the anti-CD28 monoclonal antibody (mAb) E18 or deleted CD28 expression using inducible CD28 knock-out OT-II mice as T cell donors. After injection of ovalbumin protein in adjuvant into the recipient mice we observed that systemic interferon (IFN)γ release strongly depended on CD28 costimulation of the Th1 cells, while secondary clonal expansion was not reduced in the absence of CD28 costimulation. For human memory CD4 T cell responses we also noted that cytokine release was reduced upon inhibition of CD28 costimulation. Together, our data highlight the so far underestimated role of CD28 costimulation for the reactivation of fully differentiated CD4 T cells.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 PMCID: PMC5964139 Edited by: Bernard Malissen, UMR7280 Centre d’immunologie de Marseille-Luminy (CIML), France Specialty section: This article was submitted to T Cell Biology, a section of the journal Frontiers in Immunology Reviewed by: Jacques A. Nunes, Institut National de la Santé et de la Recherche Médicale (INSERM), France; Loretta Tuosto, Sapienza Università di Roma, Italy
ISSN:	1664-3224 1664-3224
DOI:	10.3389/fimmu.2018.01060