| Abstract |
Renal cell carcinoma (RCC) cell lines were established to generate
autologous T-cell lines. With the RCC cell line MZ1257RC modified to
express the costimulatory molecule B7-1 at the cell surface, different
autologous T-cell lines were raised and characterized. The identification
of a tumor associated antigen was started using an autologous, HLA-A2
restricted T-cell clone in cDNA expression cloning. After in vitro-
sensitization of peripheral blood monocytes with the autologous RCC cell
line MZ2733RC, a HLA class I restricted T-cell line XIE6 was raised, which
lyses the autologous and various allogeneic RCC cell lines, but not the
autologous kidney cells. The T-cells express TZR-Vbeta13.6-chains and release
GM-CSF and IL-10 after antigen stimulation. Although this RCC cell line is
less sensitive towards autologous and allogeneic effector cells. Finally,
blocking of its HLA class I molecules on the cell surface enhances its
sensitivity to lymphokine activated killer cells. A reason for this may be
the expression of non-classical HLA class Ib molecules, especially HLA-G.
Seven different HLA-G transcripts were detected in RNA from carcinoma cell
lines, but not from kidney cells. In a detailed analysis, HLA-G
transcripts were found in RCC cell lines (58%), in RCC biopsies (80%) and
only in 10% of kidney epithelium biopsies. In the RCC cell line MZ2733RC a
constitutive HLA-G1 protein expression was observed, which is inducible by
IFN-gamma-treatment.
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