The immunosuppressive effect of vincristine on allostimulatory potential of human dendritic cells interferes with their function and survival.
Mature dendritic cells (mDC) are professional and potent antigen presenting cells required for initiation of primary immune responses. In the present study, we have investigated the effect of vincristine on the T cell allostimulatory potential of human monocyte-derived mDC in allogeneic mixed lymphocyte reaction. Using T lymphocytes as responding cells and mDC as stimulating cells, our data indicate that incubation of DC with vincristine decreased the accessory potency dose dependently and resulted in a subsequent inhibition of T cell proliferative responses. Treatment of mDC with vincristine also led to the alteration of their capacity to produce IL-12 but enhanced their production of IL-10. Using flow cytometry, we demonstrated that vincristine had no effect on mDC phenotype (CD83, CD40, CD86, CD58, CD54) but promoted apoptotic cell death of these cells as revealed by PI and annexin-V. These findings suggest that DC may be potential targets of cytotoxic drugs and point out the possible impairment of the immunocompetence of these cells following chemotherapy.
Rubio
M T
MT
INSERM U487 Cytokines et Immunologie des Tumeurs Humaines, IFR54, Institut Gustave Roussy, 94805 Villejuif Cedex, France.
Ittelet
D
D
Raymond
E
E
Blay
J Y
JY
Bernard
J
J
Chouaib
S
S
D015703:Antigens, CD / Q000032:analysis / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D013601:T-Lymphocytes / Q000502:physiology; D014750:Vincristine / Q000494:pharmacology*
D015703:Antigens, CD; D000972:Antineoplastic Agents, Phytogenic; D007166:Immunosuppressive Agents; D016753:Interleukin-10; D018664:Interleukin-12; D014750:Vincristine