B7 costimulatory molecules from malignant cells in patients with B‐cell chronic lymphoproliferative disorders trigger T‐cell proliferation

L Trentin, A Perin, M Siviero, F Piazza… - … Journal of the …, 2000 - Wiley Online Library
L Trentin, A Perin, M Siviero, F Piazza, M Facco, C Gurrieri, S Galvan, F Adami, C Agostini
Cancer: Interdisciplinary International Journal of the American …, 2000Wiley Online Library
BACKGROUND B7 family molecules are involved in T–B‐cell communications after
interaction with their ligands CD28 and CD152. They play a key role in costimulatory
mechanisms and during antigen presentation by efficient antigen presenting cells. B7
molecules are usually absent or expressed at low intensity on B lymphocytes from healthy
subjects. In this study, the authors addressed the questions of whether B7 molecules are
expressed and modulated in vitro on malignant B lymphocytes from patients with chronic …
BACKGROUND
B7 family molecules are involved in T–B‐cell communications after interaction with their ligands CD28 and CD152. They play a key role in costimulatory mechanisms and during antigen presentation by efficient antigen presenting cells. B7 molecules are usually absent or expressed at low intensity on B lymphocytes from healthy subjects. In this study, the authors addressed the questions of whether B7 molecules are expressed and modulated in vitro on malignant B lymphocytes from patients with chronic lymphoproliferative diseases of B‐cell type and whether they are able to trigger allogenic T‐cell reactions.
METHODS
Malignant B cells from the peripheral blood of 32 patients with B‐cell chronic lymphocytic leukemia, mantle cell lymphoma, hairy cell leukemia, and its variant form were investigated for the expression of B7 molecules on the cell surface and for the ability to trigger allogenic T lymphocytes in different experimental conditions.
RESULTS
Flow cytometry analysis demonstrated that freshly isolated malignant B cells express B7 molecules and that their expression may be up‐regulated by the in vitro triggering of the CD40 molecule. Furthermore, freshly isolated malignant B cells induce allogenic T‐cell proliferation. The in vitro triggering of malignant B lymphocytes by CD40, alone and in combination with interleukin‐4, elicits a strong allogenic T‐cell proliferation. This T‐cell proliferation is related mainly to the presence of B7 molecules on malignant and normal B lymphocytes.
CONCLUSIONS
These findings indicate that malignant B cells are efficient antigen presenting cells. It might be suggested that vaccination with pulsed malignant B cells themselves or dendritic cells with in vitro preactivated tumor B cells may represent an alternative therapeutic approach in these patients to generate an antilymphoma T‐cell response in vivo. Cancer 2000;89:1259–68. © 2000 American Cancer Society.
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