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

• Type of Material: Article
• Authors: Madhav Dhodapkar, Emory University; Ralph M. Steinman, Rockefeller University; Joseph Krasovsky, Rockefeller University; Christian Munz, Rockefeller University; Nina Bhardwaj, Rockefeller University
• Language: English
• Date: 2001-01-15
• Publisher: Rockefeller University Press
• Publication Version: Final Published Version
• Copyright Statement: © 2001 The Rockefeller University Press
• License: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1084/jem.193.2.233
• Title of Journal or Parent Work: Journal of Experimental Medicine
• ISSN: 0022-1007
• Volume: 193
• Issue: 2
• Start Page: 233
• End Page: 238
• Grant/Funding Information: This work was supported in part by an investigator award from the Cancer Research Institute (to M.V. Dhodapkar) and grants from the National Institutes of Health (CA 81138 to M.V. Dhodapkar and MO-RR00102 to the Rockefeller General Clinical Research Center). N. Bhardwaj is supported in part by the Burroughs Wellcome Fund.
• Keywords: MATURE; Science & Technology; Medicine, Research & Experimental; immunization; IMMUNITY; CD8+T cells; Life Sciences & Biomedicine; maturation; dendritic cells; tolerance; Immunology; MELANOMA; TUMOR; Research & Experimental Medicine
• Research Categories: Health Sciences, Immunology; Health Sciences, Oncology

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.