Antigen-bearing immature dendritic cells induce peptide-specific CD8(+) regulatory T cells in vivo in humans.
Regulatory T cells (T(R)s) can suppress the function of other effector T cells in the setting of autoimmunity, transplantation, and resistance to tumors. The mechanism for the induction of T(R)s has not been defined. We previously reported that an injection of immature dendritic cells (DCs) pulsed with influenza matrix peptide (MP) led 7 days later to antigen-specific silencing of effector T-cell function in the blood of 2 healthy human subjects. Here, we found that interferon-gamma-producing effectors return by 6 months. Importantly, in mixing experiments, CD8(+) T cells from the sample obtained 7 days after injection could suppress MP-specific effectors obtained before injection and those in recovery samples. This suppression or regulation was specific for the immunizing peptide (MP) and cell-dose dependent, and it required contact between the 2 samples. These data show the capacity of immature DCs to induce antigen-specific regulatory CD8(+) T cells in humans.
Dhodapkar
Madhav V
MV
Laboratory of Tumor Immunology and Immunotherapy Rockefeller University; New York, NY 10021, USA. dhodapm@mail.rockefeller.edu
Steinman
Ralph M
RM
D019264:Adoptive Transfer / Q000379:methods*; D017951:Antigen Presentation / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology; D014763:Viral Matrix Proteins / Q000276:immunology
D010446:Peptide Fragments; D014763:Viral Matrix Proteins; C448634:influenza matrix peptide (58-66); D016753:Interleukin-10; D007371:Interferon-gamma