B Lymphocyte Function in B Cell Chronic Lymphocytic Leukaemia

Wolos, Jeffrey A.; Davey, Frederick R.

doi:10.1111/j.1365-2141.1981.tb07242.x

Cited by 15 publications

(6 citation statements)

References 24 publications

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“…CLL cells show decreased expression of costimulatory molecules such as B7-1 and B7-2, resulting in an inability to provide an adequate signal 2, which is required for T-cell activation [1–3]. Equally important, T cells from CLL patients show an inverted CD4/CD8 ratio, altered cytokine production, and decreased mitogenic and allogeneic responses, despite their increased absolute numbers and enhanced expression of activation markers [3, 4].…”

Section: Discussionmentioning

confidence: 99%

“…Chronic lymphocytic leukemia (CLL) is a malignancy characterized by accumulation of clonal CD5 + B lymphocytes that are inefficient in antigen presentation [1, 2], largely due to an inadequate costimulatory capacity. The limited ability of CLL cells to present antigens to T cells is manifested as a failure to stimulate proliferation of both allogeneic and autologous T cells.…”

Section: Introductionmentioning

confidence: 99%

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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

Litzinger

Foon

Sabzevari

et al. 2008

Cancer Immunol Immunother

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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-TRICOMmodified 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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Litzinger

Foon

Sabzevari

et al. 2008

Cancer Immunol Immunother

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“…Previous studies aimed at elucidating the functional capacity of B-CLL cells have produced variable results. The majority of studies indicate that they exhibit a limited functional repertoire, including little or no activity in autologous and allogeneic mixed lymphocyte cultures (Halper et al 1979; Wolos & Davey. 1981) despite expressing HLA-Dr (Fu et al, 1979); diminiahed responses to the B-cell mitogens pokeweed, lipopolysaccharide and Epstein-Barr virus, and in antibody-dependent cellular cytotoxicity reactions (Smith et al, 1972; Gale et al, 1975: Fu et al, 1979Johnstoneet al 1982); anddecreasedin vitroimmunoglobulin synthesis (Wells & Fudenberg.…”

mentioning

confidence: 99%

Spontaneous programmed death (apoptosis) of B‐chronic lymphocytic leukaemia cells following their culture in vitro

Collins¹,

Verschuer²,

Harmon

et al. 1989

Br J Haematol

227

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Summary When B‐cell lymphocytic leukaemia (B‐CLL) cells derived from peripheral blood were cultured in vitro, a substantial proportion of them spontaneously died by apoptosis. This type of cell death is morphologically and biochemically distinct from necrosis and has previously been found to occur under physiologic and certain pathologic conditions where cell deletion appears controlled and biologically meaningful. By 30 h of culture, approximately 20% of the unfractionated B‐CLL cells were affected. There was no significant difference in the incidence of apoptosis in T‐cell depleted and undepleted cultures or when either autologous or normal human serum was used. Furthermore, seeding densities of 2 × 106 and 5 × 105 cells/ml resulted in a similar incidence of apoptosis, indicating that cell density was unlikely to be a contributing factor in producing the death. The finding that B‐CLL cells spontaneously die in vitro has at least two important implications. Firstly, previous work relating to some of the functions of B‐CLL cells and their interactions with T cells may require re‐evaluation. Secondly, an understanding of the mechanisms involved in the induction of apoptosis in this disease may have therapeutic consequences.

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“…Despite considerable therapeutic improvements throughout the last years [10–12], the disease remains incurable. CLL is characterized by a number of peculiarities: leukaemic B cells express high levels of surface MHC class I and II molecules but lack expression of important accessory and co‐stimulatory molecules [13]. As a consequence, the malignant cells successfully evade the immune system and induce tumour‐specific T‐cell anergy.…”

Section: Introductionmentioning

confidence: 99%

Engineering extracellular vesicles as novel treatment options: exploiting herpesviral immunity in CLL

Gärtner

Luckner

Wanner

et al. 2019

J of Extracellular Vesicle

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Extracellular vesicles (EVs) are important mediators of cell–cell communication. Intriguingly, EVs can be engineered and thus exploited for the targeted transfer of functional proteins of interest. Thus, engineered EVs may constitute attractive tools for the development of novel therapeutic interventions, like cancer immunotherapies, vaccinations or targeted drug delivery. Here, we describe a novel experimental immunotherapeutic approach for the adjuvant treatment of chronic lymphocytic leukaemia (CLL) based on engineered EVs carrying gp350, the major glycoprotein of Epstein–Barr virus (EBV), CD40L, a central immune accessory molecule and pp65, an immunodominant antigen of the human cytomegalovirus (CMV). We show that these engineered EVs specifically interact with malignant B cells from CLL patients and render these cells immunogenic to allogeneic and autologous EBV- and CMV-specific CD4+ and CD8+ T cells. Collectively, co-opting engineered EVs to re-target the strong herpesviral immunity in CLL patients to malignant cells constitutes an attractive strategy for the adjuvant treatment of a still incurable disease.Abbreviations: CLL: chronic lymphocytic leukaemia; EBV: Epstein-Barr virus; CMV: cytomegalovirus

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B Lymphocyte Function in B Cell Chronic Lymphocytic Leukaemia

Cited by 15 publications

References 24 publications

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

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

Spontaneous programmed death (apoptosis) of B‐chronic lymphocytic leukaemia cells following their culture in vitro

Engineering extracellular vesicles as novel treatment options: exploiting herpesviral immunity in CLL

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