In Vivo Expression of B7-1 and B7-2 By Follicular Lymphoma Cells Can Prevent Induction of T-Cell Anergy But Is Insufficient to Induce Significant T-Cell Proliferation

Abstract

Expression of B7 family costimulatory molecules on B cells defines their capacity to function as antigen presenting cells (APCs). B cells that do not express B7 costimulatory molecules induce T-cell tolerance. Therefore, the expression of B7 costimulatory molecules on malignant B cells might be critical for their recognition by anti–tumor-specific T cells. Here we show that virtually all germinal center (GC)-derived B-cell lymphomas including follicular lymphoma (FL) and diffuse large cell lymphoma, but not mantle cell lymphoma or small lymphocytic lymphomas (SLL/CLL), express B7-1 (CD80) and B7-2 (CD86) on their cell surface in situ, although at extremely low levels. Despite their expression of low levels of B7-1 and B7-2, FL cells could not induce significant allogeneic T-cell proliferation. However, B7 costimulatory molecules on FL appeared to be functional because they were capable of increasing T-cell proliferation of preactivated T cells in a secondary allogeneic mixed lymphocyte response. Moreover, low B7 expression was sufficient to prevent the induction of alloantigen-specific anergy in vitro. Therefore, we postulate that whereas low-level expression of B7 is not sufficient to initiate a productive antilymphoma T-cell response, it might be sufficient to prevent T-cell tolerance in vivo.

γ‐Ray irradiation induces B7.1 expression in myeloid leukaemic cells

“…It might suggest that the choice of B7.1 gene for a gene therapy protocol in AML would be not optimal, as substantial levels of expression of this gene could be obtained without gene transfer. However, we cannot rule out that massive transgene expression which can presently be obtained with recently described modified viral vectors targeting specific cell types could lead to a therapeutic effect because the level of B7.1 molecule expression has been reported to influence the type of immune response in lymphoma (Dilloo et al, 1997b;Dorfman et al, 1997;Gonzalez et al, 1999).…”

“…Antigen presentation by the MHC class I complex in the absence of a B7 co-stimulatory signal leads to T-cell anergy. The level of expression of B7.1 also seems to determine the type of antigen recognition by the immune system (Dorfman et al, 1997). Weak expression of B7.1 can reverse T-cell anergy against lymphoma cells, whereas its strong expression can induce an efficient cytotoxic T-cell (CTL) response.…”

The use of anti‐T‐cell receptor‐Vβ antibodies for the estimation of treatment success and phenotypic characterization of clonal T‐cell populations in cutaneous T‐cell lymphomas

“…The expression of CD80 on most of the lymphocytes in MF lesions and the co-expression of CD28 gave reason to speculate about a possible contribution of these receptors to the ongoing T-cell proliferation in MF (Nickoloff et al, 1994). Dorfman et al (1997) detected lowlevel CD80 and CD86 expression in non-Hodgkin's lymphoma cells, which failed to initiate a significant allogeneic T-cell proliferation. They postulated that low-level expression of B7 molecules is not sufficient to initiate a productive anti-lymphoma T-cell response.…”

Targeting the Immune System in Non–Small-Cell Lung Cancer: Bridging the Gap Between Promising Concept and Therapeutic Reality

“…Most cancer patients develop some degree of tumor tolerance [9], which may result from a lack of proper co-stimulatory molecules, such as B7.1 or B7.2, upon initial antigen presentation [10]. Tumor cells also evade the immune system by down-regulating immune cytokines and developing resistance to CTLs [11,12].…”