CD154 costimulation shifts the local T cell receptor repertoire not only during thymic selection but also during peripheral T-dependent humoral immune responses

Anke Faehnrich, Sebastian Klein, Arnauld Serge, Christin Nyhoegen, Sabrina Kombrink, Steffen Moeller, Karsten Keller, Juergen Westermann, Kathrin Kalies

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2 Citations (Scopus)
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Abstract

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.
Original languageEnglish
Article number1019
Number of pages11
JournalFrontiers in immunology
Volume9
DOIs
Publication statusPublished - 17 May 2018

Keywords

  • CD154 costimulation
  • T-cell repertoire
  • humoral immune response
  • sheep red blood cells
  • spleen
  • T:B-cell interaction

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