CD40 triggering of chronic lymphocytic leukemia B cells results in efficient alloantigen presentation and cytotoxic T lymphocyte induction by up-regulation of CD80 and CD86 costimulatory molecules

• Published in: Leukemia Vol. 11; no. 4; pp. 572 - 580
• Main Authors: VAN DEN HOVE, L. E, VAN GOOL, S. W, VANDENBERGHE, P, BAKKUS, M, THIELEMANS, K, BOOGAERTS, M. A, CEUPPENS, J. L
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 01.04.1997; Nature Publishing Group
• Subjects: Adhesion; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; B7-1 Antigen - analysis; Biological and medical sciences; CD25 antigen; CD4 antigen; CD40 antigen; CD40 Antigens - analysis; CD58 antigen; CD8 antigen; CD80 antigen; CD86 antigen; Cell Membrane - immunology; Cell proliferation; Chronic lymphocytic leukemia; Costimulator; CTLA-4 protein; Cytotoxicity; Fibroblasts; Fusion protein; Hematologic and hematopoietic diseases; Histocompatibility antigen HLA; Humans; Immunogenicity; Immunoglobulins; Isoantigens - analysis; Leukemia; Leukemia, Lymphoid - immunology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphatic leukemia; Lymphocytes; Lymphocytes B; Lymphocytes T; Medical sciences; Monoclonal antibodies; Priming; T-Lymphocytes, Cytotoxic - immunology; Tumor Cells, Cultured; Human; Antigen presentation; Ligand; Cytotoxicity; Stimulation; Malignant hemopathy; B-Lymphocyte; Cell surface; Antigen; Chronic; Chronic lymphocytic leukemia; Regulation(control); Alloantigen; Lymphoproliferative syndrome; T-Lymphocyte
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/sj.leu.2400598

Freshly collected chronic lymphocytic leukemia B cells (B-CLL cells) are known to be inefficient at stimulating allogeneic T cells, and to lack significant expression of B7 (CD80 and CD86) costimulatory molecules. We investigated the potential of CD40 triggering to up-regulate the expression of adhesion and costimulatory molecules on B-CLL cells, and to enhance their immunogenicity towards allogeneic T cells. B-CLL cells cocultured with human CD40 ligand-expressing mouse fibroblasts rapidly up-regulated CD54 and CD58 adhesion molecules and B7-1 (CD80) and B7-2 (CD86) costimulatory molecules, and acquired a strong stimulatory capacity towards CD4+ as well as isolated CD8+ allogeneic T cells. Costimulation by both CD80 and CD86 proved critical for allogeneic T cell proliferation and CD25 and HLA-DR expression, since these were strongly inhibited by anti-CD80 or anti-CD86 monoclonal antibodies, and completely abrogated by CTLA4-Ig fusion protein, which blocks both CD80 and CD86. B7 costimulation also proved critical for restimulation of primed B-CLL-reactive T cells. Most importantly, priming of purified CD8+ T cells with CD40-triggered allogeneic B-CLL cells resulted in cytotoxic activity against the unstimulated B-CLL cells. These findings raise the possibility that CD40 triggering of B-CLL cells might be exploited in immunotherapeutic protocols.