Blood, 15 March 2001, Vol. 97, No. 6, pp. 1750-1755
IMMUNOBIOLOGY
Idiotype-specific cytotoxic T lymphocytes in multiple
myeloma: evidence for their capacity to lyse autologous primary
tumor cells
Yue-Jin Wen,
Bart Barlogie, and
Qing Yi
From the Myeloma and Transplantation Research Center,
University of Arkansas for Medical Sciences, Little Rock, AR.
Multiple myeloma (MM) is a B-cell malignancy. The monoclonal
immunoglobulin, secreted by myeloma plasma cells, carries unique antigenic determinants (idiotype [Id]) that can be regarded as a
tumor-specific antigen. Id-based immunotherapy has been explored in
myeloma patients for the purpose of enhancing or inducing Id-specific immune responses that might lead to tumor destruction. However, despite
some evidence obtained from mouse plasmacytoma models, it is still
unclear whether Id-specific immunity may play a role in the regulation
of tumor cells in MM. In the current study, using dendritic cells (DCs)
as antigen-presenting cells, autologous Id-specific cytotoxic T
lymphocyte (CTL) lines containing both CD4+ and
CD8+ T cells were generated from myeloma patients.
The results show that Id-specific CTLs not only recognized and
lysed autologous Id-pulsed DCs but also significantly killed the
autologous primary myeloma cells. The cytotoxicity against the primary
tumor cells was major histocompatibility complex (MHC) class I- and,
to a lesser extent, class II-restricted, indicating that myeloma cells could process Id protein and present Id peptides in the context of
their surface MHC molecules. Furthermore, the CTLs lysed the target cells mainly through the perforin-mediated pathway because Concanamycin A, but not Brefeldin A
the selective inhibitors for perforin- or Fas-mediated pathwaysabrogated the cytolytic activity of
the cells. These CTLs secreted predominantly interferon-
and tumor
necrosis factor-
on antigen stimulation, indicating that they belong
to the type-1 T-cell subsets. Taken together, these findings represent
the first demonstration that Id-specific CTLs are able to lyse
autologous tumor cells in MM and, thus, provide a rationale for
Id-based immunotherapy in the disease.
