Cyclosporin A promotes spontaneous outgrowth in vitro of Epstein–Barr virus-induced B-cell lines

Bird, A. G.; McLachlan, Sandra M.; Britton, Sven

doi:10.1038/289300a0

Cited by 219 publications

(81 citation statements)

References 10 publications

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“…Evidence of monoclonality was observed in seven of these 17 patients. Five of the 17 patients, including three with monoclonal disease, received additional chemotherapy or radiotherapy, or both.…”

Section: Clinical Course and Therapymentioning

confidence: 93%

The diagnosis and treatment of posttransplant lymphoproliferative disorders

Nalesnik

Makowka

Starzl

1988

Current Problems in Surgery

238

111

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Section: Clinical Course and Therapymentioning

confidence: 93%

The diagnosis and treatment of posttransplant lymphoproliferative disorders

Nalesnik

Makowka

Starzl

1988

Current Problems in Surgery

238

111

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“…Briefly, MNC were isolated from peripheral blood as described above, and T cells were separated from B cells and monocytes by rosetting with AET erythrocytes. The rosette-negative fraction was then infected with EBV using a modification of the technique previously described (25). Supernatants from the B95-8 marmoset cell line were filtered through a 0.45-#m filter 6 (Nalge Co., Rochester, NY), diluted fourfold, and incubated with 5 x 10 cells in a sterile 12-× 74-mm tube (Falcon Labware, Oxnard, CA) for 1 h at 30°C.…”

Section: Methodsmentioning

confidence: 99%

Interleukin 2 receptors on human B cells. Implications for the role of interleukin 2 in human B cell function.

Muraguchi¹,

Kehrl²,

Longo³

et al. 1985

The Journal of Experimental Medicine

220

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It has been demonstrated (1, 2) that a number of antigen-nonspecific soluble factors exist that can transmit signals for growth and/or differentiation among lymphoid cells, particularly T lymphocytes, and may play a major role in the regulation of the immune response. Recent studies (3-5) in both murine and human systems have revealed that such antigen-nonspecific soluble factors also play a critical role in regulating the proliferation and differentiation of B iymphocytes.We have attempted to delineate the minimal and optimal signals required for the induction of resting human B cells to proliferate as well as the signals required for the induction of activated B cells to differentiate into immunoglobulinsecreting cells (4,5). In this regard~ we have recently demonstrated (6-8) that Staphylococcus aureus Cowan I (SAC) 1 or a high concentration of antiimmunoglobulin antibody that interacts with the B cell surface immunoglobulin (slg) directly induces the proliferation of resting human B cells, while a less powerful slg-mediated signal, such as that delivered by low concentrations of anti-Ig antibody, results in the activation of B cells without subsequent proliferation. These activated B cells, presumably arrested in the G1 phase of the B cell cycle, were able to respond to exogeneous T cell-derived B cell growth factor (BCGF), now designated B cell stimulatory factor (BSF) (9), to enter the S phase of the cell cycle. These activated B cells can in turn be induced to differentiate into Igsecreting cells by B cell differentiation factors (BCDF), originally referred to as T cell-replacing factors (10). These BCDF have been shown to be biochemically separable from interleukin 2 (IL-2) and BSF (11-13).It is currently controversial whether IL-2 exerts a direct effect on B cell function. Certain reports (3, 14) state that it is unlikely that IL-2 directly affects B cells; however, other studies indicate that IL-2 has an important role in the J Abbrevmtions used in this paper:

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“…SP-LCL were established by spontaneous outgrowth of PBL from EBV-seropositive donors in the presence of cyclosporin A. 11 For the establishment of these cell lines, the addition of exogenous EBV is not necessary. Briefly, 3 ϫ 10 7 peripheral blood mononuclear cells were purified by Ficoll gradient centrifugation (Pharmacia, Freiburg, Germany) and plated into 96-well plates at a density of 1 ϫ 10 6 cells/mL in RPMI 1640 (PAA Laboratories, Coelbe, Germany) supplemented with 10% fetal calf sera (FCS).…”

Section: Establishment Of Sp-lclmentioning

confidence: 99%

“…9,10 Most importantly, LCL can be easily obtained by culturing peripheral blood lymphocytes (PBL) from EBV-positive humans in vitro, because EBV-transformed B lymphocytes show a spontaneous outgrowth (SP-LCL) and can serve as a practically unlimited source of APC. 11 It was the aim of this study to determine whether and to what extent SP-LCL transfected with a tumor Ag can serve as an alternative autologous cellular vaccine for the induction of antitumoral T-cell immunity in cancer patients. To this end, SP-LCL from healthy donors and cancer patients were transfected with an episomal EBV-based expression plasmid encoding a tumor Ag.…”

mentioning

confidence: 99%

Gene-modified spontaneous Epstein-Barr virus-transformed lymphoblastoid cell lines as autologous cancer vaccines: Mutated p21 ras oncogene as a model

et al. 2000

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The transfer of genes coding for tumor antigens (Ags) into Ag-presenting cells is a promising strategy to develop cancer vaccines for patients not limited by major histocompatibility complex restriction. To test whether autologous lymphoblastoid cell lines (LCL) can be used as an alternative to dendritic cells for Ag presentation, we established LCL by spontaneous growth in cyclosporin-containing medium in vitro (SP-LCL). SP-LCL, which have an advantage over B95-8-transfected LCL in that they carry no risk of introducing a new infectious agent when used for vaccination, served as a permanent source for transfection with an episomal Epstein-Barr virus-based expression vector encoding the Ki-ras p21 oncogene carrying a point mutation at codon 12 (muRas) as a model tumor Ag. The ability of muRas-transfected SP-LCL (muRas-LCL) to induce immunoreactivity was determined in vitro. After electroporation with an optimized protocol, muRas-LCL expressed mutated ras peptides for a considerable period of time (at least 8 weeks) on the cell surface. The transfection procedure did not affect the expression of the costimulatory molecules B7.1, intercellular adhesion molecule-1, and leukocyte function associated Ag-3 by SP-LCL. muRas-LCL were able to induce muRas-specific cytotoxic T lymphocytes from three of three healthy donors and one of one patient with pancreatic carcinoma. Our results suggest that the gene transfer of muRas sequences to SP-LCL leads to an endogenous processing of this Ag in the major histocompatibility complex class I pathway and to functional presentation of antigenic peptides to CD8 ϩ T lymphocytes. Autologous SP-LCL can serve as an unlimited renewable source for autologous cellular vaccines and appear to be good candidates as presenters for a wide range of human tumor Ags.

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Cyclosporin A promotes spontaneous outgrowth in vitro of Epstein–Barr virus-induced B-cell lines

Cited by 219 publications

References 10 publications

The diagnosis and treatment of posttransplant lymphoproliferative disorders

The diagnosis and treatment of posttransplant lymphoproliferative disorders

Interleukin 2 receptors on human B cells. Implications for the role of interleukin 2 in human B cell function.

Gene-modified spontaneous Epstein-Barr virus-transformed lymphoblastoid cell lines as autologous cancer vaccines: Mutated p21 ras oncogene as a model

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