Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells.
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, injection 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 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 or microbial immunity.
Dhodapkar
M V
MV
Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, New York 10021, USA. dhodapm@rockvax.rockefeller.edu
Steinman
R M
RM
Krasovsky
J
J
Munz
C
C
Bhardwaj
N
N
D000328:Adult; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000637:transplantation*; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D007114:Immunization / Q000379:methods; D007156:Immunologic Memory; D066298:In Vitro Techniques; D007271:Injections, Intradermal; D007279:Injections, Subcutaneous; D009975:Orthomyxoviridae / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014182:Transplantation, Autologous; D014763:Viral Matrix Proteins / Q000276:immunology
D014763:Viral Matrix Proteins; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin