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Blood, Vol. 92 No. 5 (September 1), 1998:
pp. 1677-1684
CD80-Transfected Acute Myeloid Leukemia Cells Induce Primary
Allogeneic T-Cell Responses Directed at Patient Specific Minor
Histocompatibility Antigens and Leukemia-Associated Antigens
Tuna Mutis,
Ellen Schrama,
Cornelis J.M. Melief, and
Els Goulmy
From the Department of Immunohematology and Blood Bank, Leiden
University Medical Center, Leiden, The Netherlands.
Despite sufficient levels of HLA class I and class II expression,
acute myeloid leukemia (AML) cells usually fail to induce a significant
T-cell response in vitro. Therefore, we investigated whether in vitro
modifications could enhance the T-cell stimulatory properties of AML
cells. AML cells were either cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-4 (IL-4), and tumor
necrosis factor- (TNF-), or transfected with the CD80 (B7.1) gene
and used as stimulator cells for primed and unprimed allogeneic T
cells. Cytokine treatment increased HLA class I and II expression, but
did not induce CD80 on AML cells. Cytokine-treated AML cells
efficiently presented nominal and allo-antigens to primed T-cell
clones, induced strong T-cell proliferation in HLA mismatched mixed
lymphocyte reactions (MLR), but failed to induce primary T-cell
responses from an HLA identical bone marrow donor in MLR. In contrast,
CD80-transfected AML cells induced T-cell proliferation of
HLA-identical bone marrow donor peripheral blood mononuclear cell
(PBMC) in primary MLR, allowing the generation of leukemia reactive
CD4+ T-cell lines and clones. The majority of the
generated oligoclonal (25 of 35) T-cell cultures showed patient
specific reactivity that did not discriminate between patient's
leukemic cells and Epstein-Barr virus (EBV)-transformed B cells
(EBV-LCL). The remaining 10 oligoclonal T-cell cultures recognized only
leukemic cells. One of these latter leukemia reactive oligoclonal T
cells was cloned. The majority of the clones (25 of 29) reacted against both leukemic cells and patient's EBV-LCL. A minority of the T-cell clones with the CD4 phenotype (four of 29) showed strong
HLA-DP restricted reactivity against leukemic cells, but
not against patient's EBV-LCL or against HLA-matched nonleukemic
cells, indicating that their target antigens are preferentially
expressed by leukemic cells. In conclusion, our study shows that the in
vitro allogeneic T-cell response induced by CD80-transfected AML cells
is mainly directed against patient's specific minor histocompatibility
antigens, while antigens preferentially expressed by leukemic cells can also trigger T-cell responses.
© 1998 by The American Society of Hematology.
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