DIFFERENTIATION OF HUMAN LEUKEMIC DENDRITIC
DELLS FROM AML LINE HL-60
Zhou JF, Yang XQ, Li X
Department of Immunology, The Children
Hospital, Chongqing, China
Objective:
Human
leukemic cells share the ontogeny of professional antigen presenting cells
(APC).The capacity of leukemic cells to present endogenously expressed
tumor-associated antigendirectly to T cells has been the focus. Evidences
suggest specific cytokine or other agents can enhance APC function. We
therefore investigated the response of less-mature myeloid cells (HL-60) to
the agents including protein kinase C activator-phorbol ester
(PMA),granulocyte-macrophage-colony timulating factor (GM-CSF), tumor
necrosis factor-alpha (TNF-α) and interleukin4 (IL-4).
Methods: The promyelocytic leukemia line HL-60 was treated by
granulocyte-macrophage csf(50ng/ml) plus tumor necrosis factor –α (2.5ng/ml), phorbol ester
(10ng/ml).Morphologic and phenotypic characteristics of the treated cells
were observed. The cells induced specific cytotoxic T lymphocytes. The
killing activity of CTL in vitro was tested by the method of 3H-TdR
release assay.
Results: After culturing with GM -CSF , TNF-αand IL-4 for15 days, small
fraction manifested dentritic cell -like morphology .The expression of CD1a
was aroused to 14 percent. The co stimulatory molecules CD86 increased 36
percent and CD80 remained negative. Development of the DC was pronounced
with GM -CSF plus TNF-α→PMA→GM -CSF plus TNF-αfor 7-11 days. CD1a
reached 20 percent. CD86 and CD80 was 72% and 19 % separately. HL-60
proliferation was suppressed by these factories and apoptosis was triggered
within 24h by PMA or TNF-αalone. The specific tumor-lyses capability of
CTL activated by treated HL-60 increased significantly.
Conclusion: It is verified that in vitro human AML precursors
can be differentiated into enhanced APC.And this phenomenon could be
utilized for immunotherapy aimed at enhancing presentation of leukemia
antigens to T cells.