title: Chronic lymphocytic leukemia (CLL) cells genetically modified to express B7-1, ICAM-1, and LFA-3 confer APC capacity to T cells from CLL patients.
abstract: In chronic lymphocytic leukemia (CLL), malignant B cells and nonmalignant T cells exhibit dysfunction. We previously demonstrated that infection of CLL cells with modified vaccinia Ankara (MVA) expressing the costimulatory molecules B7-1, ICAM-1, and LFA-3 (designated TRICOM) increased expression of these costimulatory molecules on the surface of CLL cells and thus augmented their antigen-presenting capability. Here, we evaluate the effect of MVA-TRICOM-modified CLL cells on T cells. Following incubation with irradiated MVA-TRICOM-modified CLL cells, allogeneic and autologous CD4(+) and CD8(+) T cells expressed significantly higher levels of B7-1, ICAM-1, and LFA-3. We show that this increase was the result of physical acquisition from the antigen-presenting cells (APCs), and that purified T cells that acquired costimulatory molecules from MVA-TRICOM-modified CLL cells were able to stimulate the proliferation of untreated T cells. These results demonstrate for the first time that T cells from CLL patients can acquire multiple costimulatory molecules from autologous CLL cells and can then act as APCs themselves. Given the immunodeficiencies characteristic of CLL, enhancing the antigen-presenting function of CLL cells and T cells simultaneously could be a distinct advantage in the effort to elicit antitumor immune responses.
authors.affiliation: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Mary T
authors.initials: MT
authors.lastname: Litzinger
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Foon
authors.forename: Helen
authors.initials: H
authors.lastname: Sabzevari
authors.forename: Kwong-Yok
authors.initials: KY
authors.lastname: Tsang
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Schlom
authors.forename: Claudia
authors.initials: C
authors.lastname: Palena
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology*; D018122:B7-1 Antigen / Q000235:genetics / Q000378:metabolism*; D018968:CD58 Antigens / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014616:Vaccinia virus / Q000235:genetics
chemical_list: D018122:B7-1 Antigen; D018968:CD58 Antigens; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1