CD154 Costimulation Shifts the Local T-Cell Receptor Repertoire Not Only During Thymic Selection but Also During Peripheral T-Dependent Humoral Immune Responses

• Published in: Frontiers in immunology 2018-05, Vol.9, p.1019-1019
• Main Authors: Fähnrich, Anke, Klein, Sebastian, Sergé, Arnauld, Nyhoegen, Christin, Kombrink, Sabrina, Möller, Steffen, Keller, Karsten, Westermann, Jürgen, Kalies, Kathrin
• Format: Article
• Language: English
• Subjects: Animals; Antigen-Presenting Cells - immunology; CD154 costimulation; CD4-Positive T-Lymphocytes - immunology; CD40 Antigens - genetics; CD40 Antigens - immunology; CD40 Ligand - genetics; CD40 Ligand - immunology; Cell Differentiation - immunology; High-Throughput Nucleotide Sequencing; humoral immune response; Immunity, Humoral; Immunology; Life Sciences; Lymphocyte Activation - immunology; Mice; Receptors, Antigen, T-Cell, alpha-beta - genetics; Receptors, Antigen, T-Cell, alpha-beta - immunology; sheep red blood cells; Signal Transduction - immunology; spleen; Spleen - anatomy & histology; Spleen - immunology; T-cell repertoire; T:B-cell interaction; Th2 Cells - enzymology; Th2 Cells - immunology
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2018.01019

CD154 is a transmembrane cytokine expressed transiently on activated CD4 T cells upon T-cell receptor (TCR) stimulation that interacts with CD40 on antigen-presenting cells. The signaling via CD154:CD40 is essential for B-cell maturation and germinal center formation and also for the final differentiation of CD4 T cells during T-dependent humoral immune responses. Recent data demonstrate that CD154 is critically involved in the selection of T-cell clones during the negative selection process in the thymus. Whether CD154 signaling influences the TCR repertoire during peripheral T-dependent humoral immune responses has not yet been elucidated. To find out, we used CD154-deficient mice and assessed the global TCRβ repertoire in T-cell zones (TCZ) of spleens by high-throughput sequencing after induction of a Th2 response to the multiepitopic antigen sheep red blood cells. Qualitative and quantitative comparison of the splenic TCZ-specific TCRβ repertoires revealed that CD154 deficiency shifts the distribution of Vβ-Jβ genes after antigen exposure. This data led to the conclusion that costimulation via CD154:CD40 during the interaction of T cells with CD40-matured B cells contributes to the recruitment of T-cell clones into the immune response and thereby shapes the peripheral TCR repertoire.