Ultrastructural basis of enhanced antitumor cytotoxicity of cord blood-derived CTLs: a comparative analysis with peripheral blood and bone marrow.
Umbilical cord blood cells (UCBC) are a rich source of immature immune effector and accessory cells, including dendritic cells. UCBC-derived cytotoxic T lymphocytes (CTLs) generated against human breast cancer or neuroblastoma have shown an increased tumor-specific cytotoxicity compared to peripheral blood (PB)-derived CTLs. The precise mechanism of this increased cytotoxicity is not known. Since dendritic cells (DCs) play a central role in the immunostimulation, we compared the ultrastructure and antigen presenting nature of DCs from UCBC, PB and bone marrow (BM) at various stages of maturation using scanning and transmission electron microscopy as well as fluorescent microscopy to elucidate the mechanism underlying the increased cytotoxicity of UCBC-derived CTLs. DCs were examined for their immunophenotype nuclear morphology, dendritic processes and cytoplasmic endosomal vesicles after 0, 3, 7 and 10 days in culture with antigen priming on day 6. Results showed that there were smaller and more vesicles in UCB-DCs compared to DCs from the other two sources, while the endosomal vesicles in PB-DCs were heterogenous in size. The antigen processing ability of the UCB-DCs showed an increase in antigen-positive endosomes compared to PB-DCs as determined by the fluorescent microscopy. Thus, our results provided the comparative analyses of DCs from cord blood, peripheral blood and bone marrow, and suggested that UCBC-DCs might have better antigen presenting ability leading to increased CTL-mediated antitumor cytotoxicity.
Clark
Erin M
EM
Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Joshi
Deepa S
DS
Grimm
Andrew B
AB
Joshi
Avadhut D
AD
Wang
Peng
P
Joshi
Shantaram S
SS
D017951:Antigen Presentation / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology* / Q000648:ultrastructure; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology*; D006801:Humans; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D009369:Neoplasms / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000648:ultrastructure