Bcl-2 transfection protects Hut78 cell line from different types of cytotoxic effector cells

Saxena, Rajiv K.; Collins, Gary D.; Chrest, Joseph; Adler, William H.

doi:10.1016/0165-2478(96)02590-4

Cited by 3 publications

(2 citation statements)

References 12 publications

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“…We have recently reported the faster lysis kinetics of CTLs from elderly C57BL/6J mice after polyclonal stimulation with anti-CD3/CD28 beads (Zöphel et al, 2022). Increased cytotoxicity with age has also been observed in concanavalin Aactivated splenocytes (Saxena & Adler, 1999;Saxena et al, 1988).…”

Section: Discussionmentioning

confidence: 93%

“…The impaired expansion of antigen-specific CD8 + T cells and decreased expression of effector molecules further contribute to inefficient pathogen clearance in elderly humans and mice (Jergović et al, 2019;Smithey et al, 2011). However, despite the overall reduced T-cell response, we and others have revealed growing evidence that CD8 + T cells' intrinsic cytotoxic capacity increases with age (Saxena & Adler, 1999;Saxena et al, 1988;Zöphel et al, 2022). Separating cell-intrinsic capabilities from microenvironmental changes may open new opportunities for developing and improving immunotherapeutic approaches.…”

Section: Introductionmentioning

confidence: 99%

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Heterozygous OT‐I mice reveal that antigen‐specific CD8⁺ T cells shift from apoptotic to necrotic killers in the elderly

et al. 2023

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Numerous alterations in CD8 + T cells contribute to impaired immune responses in elderly individuals. However, the discrimination between cell-intrinsic dysfunctions and microenvironmental changes is challenging. TCR transgenic OT-I mice are utilized to investigate CD8 + T-cell immunity, but their immunodeficient phenotype hampers their use especially in aging. Here, we demonstrate that using a heterozygous OT-I model minimizes the current limitations and provides a valuable tool to assess antigen-specific T-cell responses even at old age. We analyzed phenotypic and functional characteristics of CD8 + T cells from OT-I +/+ and OT-I +/− mice to prove the applicability of the heterozygous system. Our data reveal that OVA-activated CD8 + T cells from adult OT-I +/− mice proliferate, differentiate, and exert cytolytic activity equally to their homozygous counterparts. Moreover, common age-related alterations in CD8 + T cells, including naive T-cell deterioration and decreased proliferative capacity, also occur in elderly OT-I +/− mice, indicating the wide range of applications for in vivo and in vitro aging studies. We used the OT-I +/− model to investigate cell-intrinsic alterations affecting the cytotoxic behavior of aged CD8 + T cells after antigen-specific in vitro activation. Time-resolved analysis of antigen-directed target cell lysis confirmed previous observations that the cytotoxic capacity of CD8 + T cells increases with age.Surprisingly, detailed single cell analysis revealed that transcriptional upregulation of perforin in aged CD8 + T cells shifts the mode of target cell death from granzymemediated apoptosis to rapid induction of necrosis. This unexpected capability might be beneficial or detrimental for the aging host and requires detailed evaluation.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Heterozygous OT‐I mice reveal that antigen‐specific CD8⁺ T cells shift from apoptotic to necrotic killers in the elderly

et al. 2023

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Bcl-2 and c-Myc co-operate in the Epstein – Barr virus-immortalized human B-cell line GM607 but do not confer tumorigenicity

Tomlin

Guinn

Penn

et al. 2005

Leukemia & Lymphoma

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Eighty-five percent of follicular lymphomas possess a characteristic t(14;18) translocation that results in the deregulated expression of the proto-oncogene BCL-2. BCL-2 overexpression alone is insufficient for full cellular transformation and at least 1 other genetic event is believed to be necessary for follicular lymphoma development. Deregulated c-Myc expression has previously been shown to cooperate with Bcl-2 to transform murine fibroblast cell lines and lead to tumor development in mice. We have developed a human model system to study early transformation in lymphoid cells using immortalized lymphoblastoid cells. We sequentially introduced BCL-2 and c-MYC, 2 proto-oncogenes known to be involved in the transformation of B cells into Epstein-Barr virus (EBV)-immortalized human B cells. We show that the c-Myc and Bcl-2 overexpression, together with EBV immortalization were insufficient to cause full cellular transformation as measured by cell proliferation rates, soft agar and tumorigenicity assays. These results show that more than 3 genetic hits (EBV infection, Bcl-2 and c-Myc overexpression) were required for the full cellular transformation of human lymphoblastoid cells. However, subtle changes in cellular proliferation and sensitivity to apoptosis were documented, at non-limiting dilutions. These changes may confer a susceptibility to the modified cells such that they are more susceptible to the acquisition of additional genetic changes and evolve towards a fully transformed state. In addition, the model system developed may be suitable for the identification of further known and novel oncogenic events involved in the full transformation of B cells.

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Apoptosis and Cell Proliferation Capacity in AKR Lymphoma Malignancy Variants

Donin

Sinai

et al. 2000

Cancer Investigation

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Dysregulation in apoptotic cell death has recently emerged as a factor in tumorigenesis, but its effect in tumor progression is not yet established. In the present study we evaluated the levels of proliferative and apoptotic cell fractions in a T-cell lymphoma tumor progression model. We compared these features and the expression of apoptosis-related genes in primary tumors of several AKR lymphoma malignancy variants. According to DNA flow cytometry, a considerable proportion of cells (35-40%) was in the proliferative (S + G2/M) phase in all variants, but a slight augmentation with increasing malignancy was noted. Apoptotic cell content was, unexpectedly, the lowest in the less malignant variant. This might be due to the higher content in macrophages observed in this variant, which possibly partly eliminated apoptotic bodies. We found an increase in bcl-2 level with increasing malignancy that was probably counterbalanced by the simultaneous increase observed in the Fas receptor.

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Bcl-2 transfection protects Hut78 cell line from different types of cytotoxic effector cells

Cited by 3 publications

References 12 publications

Heterozygous OT‐I mice reveal that antigen‐specific CD8⁺ T cells shift from apoptotic to necrotic killers in the elderly

Heterozygous OT‐I mice reveal that antigen‐specific CD8⁺ T cells shift from apoptotic to necrotic killers in the elderly

Bcl-2 and c-Myc co-operate in the Epstein – Barr virus-immortalized human B-cell line GM607 but do not confer tumorigenicity

Apoptosis and Cell Proliferation Capacity in AKR Lymphoma Malignancy Variants

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Bcl-2 transfection protects Hut78 cell line from different types of cytotoxic effector cells

Cited by 3 publications

References 12 publications

Heterozygous OT‐I mice reveal that antigen‐specific CD8+ T cells shift from apoptotic to necrotic killers in the elderly

Heterozygous OT‐I mice reveal that antigen‐specific CD8+ T cells shift from apoptotic to necrotic killers in the elderly

Bcl-2 and c-Myc co-operate in the Epstein – Barr virus-immortalized human B-cell line GM607 but do not confer tumorigenicity

Apoptosis and Cell Proliferation Capacity in AKR Lymphoma Malignancy Variants

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Heterozygous OT‐I mice reveal that antigen‐specific CD8⁺ T cells shift from apoptotic to necrotic killers in the elderly

Heterozygous OT‐I mice reveal that antigen‐specific CD8⁺ T cells shift from apoptotic to necrotic killers in the elderly