[Mechanism of augmented anti-tumor immunity in reconstituted lymphopenic mice immunized with melanoma vaccine].
OBJECTIVE
To explore mechanisms of the augmented anti-tumor immunity observed in reconstituted lymphopenic mice (RLM) receiving melanoma vaccination.


METHODS
The study is to investigate the anti-tumor immunity of tumor vaccination during early immune reconstitution period following irradiation and cyclophosphamide (CY)-induced lymphopenia. Lymphopenic mice were subsequently reconstituted with naive splenocytes from syngeneic mice and immunized with irradiated melanoma cells F10 (irradiation experiment) and GM-CSF-modified D5 melanoma cells (D5-G6) (CY experiment). Controls included normal C57BL/6 mice receiving the corresponding vaccination, un-immunized naive mice and RLM. 8 - 10 days after vaccination, tumor vaccine draining lymph nodes (TVDLN) were harvested and phenotyped by FACS analysis. T cells purified from TVDLN were stimulated with anti-CD3 and anti-TCRbeta and proliferation was assessed by [(3)H]-TdR incorporation and FACS assay was performed for CD69 expression.


RESULTS
The augmented anti-tumor immunity correlated with a significant increase in the percentage of T cells with activation/memory phenotype in the TVDLN of vaccinated RLM, compared to that of the controls. There was also a significant increase in the density of DCs in TVDLNs. The activation threshold of T cells generated from vaccinated RLM was significantly decreased, resulting in markedly enhanced proliferating capability upon anti-CD3 stimulation.


CONCLUSIONS
This study suggests that the augmented anti-tumor immunity observed in vaccinated RLM is due to down regulated activation threshold of T cells during lymphopenia-driven T cell proliferation, which may in turn facilitate the breaking down of immune tolerance to weak tumor antigens upon vaccination with tumor cell vaccines.
Ma
Jun
J
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute for Cancer Research, School of Life Science & Technology, Xi'an Jiaotong University, Xi'an, 710061, China.
Wang
Yi-li
YL
Hu
Hong-ming
HM
Fox
Bernard A
BA
Si
Lü-sheng
LS
D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage*; D003520:Cyclophosphamide; D008198:Lymph Nodes / Q000276:immunology; D008231:Lymphopenia / Q000209:etiology / Q000276:immunology*; D008297:Male; D008546:Melanoma, Experimental / Q000276:immunology* / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology*; D014916:Whole-Body Irradiation
D019496:Cancer Vaccines; D003520:Cyclophosphamide