Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells

Madhav V. Dhodapkar, Ralph M. Steinman, Joseph Krasovsky, Christian Munz, Nina Bhardwaj

Research output: Contribution to journalArticlepeer-review

1224 Scopus citations

Abstract

Immunostimulatory properties of dendritic cells (DCs) are linked to their maturation state. Injection of mature DCs rapidly enhances antigen-specific CD4+ and CD8+ T cell immunity in humans. Here we describe the immune response to a single injection of immature DCs pulsed with influenza matrix peptide (MP) and keyhole limpet hemocyanin (KLH) in two healthy subjects. In contrast to prior findings using mature DCs, rejection of immature DCs in both subjects led to the specific inhibition of MP-specific CD8+ T cell effector function in freshly isolated T cells and the appearance of MP-specific interleukin 10-producing cells. When pre-and postimmunization T cells were boosted in culture, there were greater numbers of MP-specific major histocompatibility complex tetramer-binding cells after immunization, but these had reduced interferon γ production and lacked killer activity. These data demonstrate the feasibility of antigen-specific inhibition of effector T cell function in vivo in humans and urge caution with the use of immature DCs when trying to enhance tumor microbial immunity.

Original languageEnglish
Pages (from-to)233-238
Number of pages6
JournalJournal of Experimental Medicine
Volume193
Issue number2
DOIs
StatePublished - 15 Jan 2001
Externally publishedYes

Keywords

  • CD8 T cells
  • Dendritic cells
  • Immunization
  • Maturation
  • Tolerance

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