Deficient T(H)-1 responses from TNF-alpha-matured and alpha-CD40-matured dendritic cells

J Immunother. Feb-Mar 2008;31(2):157-65. doi: 10.1097/CJI.0b013e31815eb0df.

Abstract

The ultimate success of dendritic cell (DC) vaccination for the active immunotherapy of neoplasia is thought to be dependent on a very large number of variables, including DC generation protocol, loading methodology, dose, route of administration, and maturation method. Although the use of a maturation cocktail comprising interleukin (IL)-1beta, tumor necrosis factor-alpha, IL-6, and prostaglandin E2 (ITIP) has recently appeared in the literature, much of the data in the basic and clinical literature have been generated using DCs matured with the single inflammatory cytokine TNF-alpha. Here, we demonstrate that DCs matured with TNF-alpha alone or in combination with CD40 agonism are highly deficient, both physiologically and functionally, in comparison with DCs matured with IL-1beta, TNF-alpha, IL-6, and prostaglandin E2. Empirically, the data suggest that DCs matured with these agents are deficient in the induction of type 1 T-helper responses. We further speculate that DCs matured by these methods might be suboptimal for the priming of naive responses.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • Antigens, CD / metabolism
  • CD40 Antigens / agonists*
  • CD40 Antigens / immunology
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Differentiation / drug effects*
  • Cell Differentiation / immunology
  • Cell Proliferation / drug effects
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Dinoprostone / pharmacology
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-12 / metabolism
  • Interleukin-1beta / pharmacology
  • Interleukin-6 / pharmacology
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology*

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • CD40 Antigens
  • Interleukin-1beta
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-12
  • Interferon-gamma
  • Dinoprostone