Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 645-653 |
| Number of pages | 9 |
| Journal | International Journal of Oncology |
| Volume | 37 |
| Issue number | 3 |
| DOIs | |
| State | Published - Sep 2010 |
| Externally published | Yes |
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Keywords
- Antigen processing
- Bone marrow
- Cord blood
- Dendritic cells
- Peripheral blood
- Ultrastructure
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Ultrastructural basis of enhanced antitumor cytotoxicity of cord blood-derived CTLs : A comparative analysis with peripheral blood and bone marrow. / Clark, Erin M.; Joshi, Deepa S.; Grimm, Andrew B.; Joshi, Avadhut D.; Wang, Peng; Joshi, Shantaram S.
In: International Journal of Oncology, Vol. 37, No. 3, 09.2010, p. 645-653.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Ultrastructural basis of enhanced antitumor cytotoxicity of cord blood-derived CTLs
T2 - A comparative analysis with peripheral blood and bone marrow
AU - Clark, Erin M.
AU - Joshi, Deepa S.
AU - Grimm, Andrew B.
AU - Joshi, Avadhut D.
AU - Wang, Peng
AU - Joshi, Shantaram S.
PY - 2010/9
Y1 - 2010/9
N2 - 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.
AB - 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.
KW - Antigen processing
KW - Bone marrow
KW - Cord blood
KW - Dendritic cells
KW - Peripheral blood
KW - Ultrastructure
UR - http://www.scopus.com/inward/record.url?scp=77956527811&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77956527811&partnerID=8YFLogxK
U2 - 10.3892/ijo-00000713
DO - 10.3892/ijo-00000713
M3 - Article
C2 - 20664933
AN - SCOPUS:77956527811
VL - 37
SP - 645
EP - 653
JO - International Journal of Oncology
JF - International Journal of Oncology
SN - 1019-6439
IS - 3
ER -