Transfection of B7-1 cDNA empowers antigen presentation of blood malignant cells for activation of anti-tumor T cells.
OBJECTIVE
To define roles of B7-1 co-stimulation factor expressed in human malignant cell lines in mediating anti-tumor T cell immune responses.


METHODS
Examining human leucocyte antigen (HLA) and B7 expressions on 8 human blood malignancies cell lines by flow cytometry. Transfecting B7-1 gene to B7-1 negative (B7(-)) Raji and B7(-) Jurkat cell lines by liposome, and comparing the potencies of blood malignant cell lines in the induction of T cell activation by examination of T cell cytokine mRNAs before and after transfection using semi-quantitative reverse transcription polymerase chain reaction (RT-PCR).


RESULTS
High level of HLA I and II molecules were expressed in most human blood malignant cell lines examined, and the co-stimulatory factor B7-2 was also highly expressed. In contrast, another member of B7 family: B7-1 was either not expressed or very limitedly expressed in most of these hematopoietic malignant cell lines. Most importantly, transfection of B7-1 gene to B7(-). Raji and B7(-). Jurkat cell lines made these cell lines better antigen presenting cells for stimulation of anti-tumor T cell activation, which was demonstrated by up regulation of expression of T cell cytokines IL-2, IL-4 and INF-gamma mRNAs after incubation of these tumor cells with T cells for 24 h.


CONCLUSIONS
B7 co-stimulation plays an important role in anti-tumor immunity. Transfection of B7-1 gene to the human hematopoietic malignant cell lines that are deficient in the B7-1 expression empowers their antigen presentation potency for activation of anti-tumor T cells. Our results suggested that repairing the deficiency of B7-1 co-stimulatory pathway in tumor cells might be a novel immunotherapeutic approach for human hematopoietic malignancies.
Ke
Xiaoyan
X
Department of Hematology, Third Hospital, Peking University, Beijing 100083, China. xiaoyank@yahoo.com
Jia
Liping
L
Wang
Jing
J
Wang
Debing
D
D017951:Antigen Presentation; D015703:Antigens, CD / Q000032:analysis; D018122:B7-1 Antigen / Q000032:analysis / Q000502:physiology*; D051940:B7-2 Antigen; D016207:Cytokines / Q000235:genetics; D005434:Flow Cytometry; D015809:HLA-DR7 Antigen / Q000502:physiology; D019337:Hematologic Neoplasms / Q000276:immunology*; D006801:Humans; D020014:K562 Cells; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection; D020298:U937 Cells
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D016207:Cytokines; D015809:HLA-DR7 Antigen; D008562:Membrane Glycoproteins; D012333:RNA, Messenger