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Blood, Vol. 93 No. 6 (March 15), 1999:
pp. 1992-2002
CD40-Activated B-Cell Chronic Lymphocytic Leukemia Cells for Tumor
Immunotherapy: Stimulation of Allogeneic Versus Autologous T Cells
Generates Different Types of Effector Cells
Raymund Buhmann,
Annette Nolte,
Doreen Westhaus,
Bertold Emmerich, and
Michael Hallek
From the Laboratorium für Molekulare Biologie, Genzentrum,
Medizinische Klinik, Klinikum Innenstadt, and Medizinische Klinik III,
Klinikum Gro hadern, Ludwig-Maximilians-Universität,
München, Germany.
Although spontaneous remissions may rarely occur in B-cell chronic
lymphocytic leukemia (B-CLL), T cells do generally not develop a
clinically significant response against B-CLL cells. Because this
T-cell anergy against B-CLL cells may be caused by the inability of
B-CLL cells to present tumor-antigens efficiently, we examined the
possibility of upregulating critical costimulatory (B7-1 and B7-2) and
adhesion molecules (ICAM-1 and LFA-3) on B-CLL cells to improve antigen
presentation. The stimulation of B-CLL cells via CD40 by culture on
CD40L expressing feeder cells induced a strong upregulation of
costimulatory and adhesion molecules and turned the B-CLL cells into
efficient antigen-presenting cells (APCs). CD40-activated B-CLL
(CD40-CLL) cells stimulated the proliferation of both
CD4+ and CD8+ T cells. Interestingly,
stimulation of allogeneic versus autologous T cells resulted in the
expansion of different effector populations. Allogeneic CD40-CLL cells
allowed for the expansion of specific CD8+
cytolytic T cells (CTL). In marked contrast, autologous CD40-CLL cells
did not induce a relevant CTL response, but rather stimulated a
CD4+, Th1-like T-cell population that expressed high
levels of CD40L and released interferon- in response to stimulation
by CD40-CLL cells. Together, these results support the view that CD40
activation of B-CLL cells might reverse T-cell anergy against the
neoplastic cell clone, although the character of the immune response
depends on the major histocompatibility complex (MHC)
background on which the CLL or tumor antigens are presented. These
findings may have important implications for the design of cellular
immunotherapies for B-CLL.
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