Defective Th1 and Th2 cytokine synthesis in the T-T cell presentation model for lack of CD40/CD40 ligand interaction

Lucrezia De Vita, Daniele Accapezzato, Giorgio Mangino, Stefania Morrone, Isabella Santilio, Marco Antonio Casciaro, Danila Fava, Guglielmo Bruno, Gianfranco Del Prete, Angela Santoni, Vincenzo Barnaba

Research output: Contribution to journalArticlepeer-review

Abstract

In this study, T or NK cell clones used as antigen-presenting cells (T- or NK-APC) were shown to be significantly less efficient than professional APC in inducing Th1 and Th2 cytokines by antigen-specific T cell clones. This phenomenon was not related to a limited engagement of TCR by T-APC, since comparable thresholds of TCR down-regulation were shown when antigen was presented by either T-APC or professional APC. Rather, the stimulatory T-APC weakness was due to their inability, because they are CD40-, to provide the appropriate co-stimuli to responder T cells both indirectly via IL-12, and partially via direct CD40L triggering on T cells. Indeed, the simultaneous addition of IL-12 and reagents directly engaging CD40L on responder T cells restored T cell cytokine synthesis when antigen was presented by T-APC. In addition, either IL-12 production or blocking of T cell cytokine synthesis by anti-IL-12 p75 antibodies was evident only when professional APC were used in our antigen-specific system. The down-regulation of cytokine synthesis in the system of T-T cell presentation could represent a novel mechanism of immune regulation, which may intervene to switch off detrimental Th1- or Th2-mediated responses induced by antigen presentation among activated T cells infiltrating inflamed tissues.

Original languageEnglish
Pages (from-to)3552-3563
Number of pages12
JournalEuropean Journal of Immunology
Volume28
Issue number11
DOIs
Publication statusPublished - Nov 1998

Keywords

  • Antigen presentation
  • Co-stimulatory molecules
  • Cytokine
  • Th1
  • Th2

ASJC Scopus subject areas

  • Immunology

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