Activated T Cell Death In Vivo Mediated by Proapoptotic Bcl-2 Family Member Bim

Hildeman, David A.; Zhu, Yanan; Mitchell, Thomas C.; Bouillet, Philippe; Strasser, Andreas; Kappler, John W.; Marrack, Philippa

doi:10.1016/s1074-7613(02)00322-9

Cited by 514 publications

(620 citation statements)

References 50 publications

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“…11,14,30 This prior work has been complicated by potential non-T-cell autonomous role of Bim and the ongoing autoimmune disease in Bim-deficient mice due to altered thymic selection. Importantly, T-cell-specific loss of Bim recapitulates the T-cell phenotype of mice with germline loss of Bim.…”

Section: Discussionmentioning

confidence: 99%

Bim controls IL-15 availability and limits engagement of multiple BH3-only proteins

Kurtuluş

Sholl

et al. 2014

Cell Death Differ

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During the effector CD8 þ T-cell response, transcriptional differentiation programs are engaged that promote effector T cells with varying memory potential. Although these differentiation programs have been used to explain which cells die as effectors and which cells survive and become memory cells, it is unclear if the lack of cell death enhances memory. Here, we investigated effector CD8 þ T-cell fate in mice whose death program has been largely disabled because of the loss of Bim. Interestingly, the absence of Bim resulted in a significant enhancement of effector CD8 þ T cells with more memory potential. Bim-driven control of memory T-cell development required T-cell-specific, but not dendritic cell-specific, expression of Bim. Both total and T-cell-specific loss of Bim promoted skewing toward memory precursors, by enhancing the survival of memory precursors, and limiting the availability of IL-15. Decreased IL-15 availability in Bim-deficient mice facilitated the elimination of cells with less memory potential via the additional pro-apoptotic molecules Noxa and Puma. Combined, these data show that Bim controls memory development by limiting the survival of pre-memory effector cells. Further, by preventing the consumption of IL-15, Bim limits the role of Noxa and Puma in causing the death of effector cells with less memory potential.

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Section: Discussionmentioning

confidence: 99%

Bim controls IL-15 availability and limits engagement of multiple BH3-only proteins

Kurtuluş

Sholl

et al. 2014

Cell Death Differ

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“…12 In the immune system Bim is required for deletion of autoreactive B and T cells 13,14 and cessation of acute T-cell responses in vivo. 15,16 Bim-deficient B and T cells die normally in response to FasL but BimÀ/À T cells exhibit reduced sensitivity to dexamethasone, ionomycin and g-irradiation. However, the most striking phenotype is the resistance of both B and T cells to cytokine deprivation.…”

Section: Bim As a Sensor Of Survival Factors And Trophic Supportmentioning

confidence: 99%

Regulatory phosphorylation of Bim: sorting out the ERK from the JNK

et al. 2005

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“…Correlation of daughter cell loss with decreased expression of Bcl-2 T cells stimulated by superantigens in vivo rapidly lose Bcl-2 expression [9,11,18,27,28]. To determine if the same was true of peptide-stimulated DO11.10 T cells, splenocytes were harvested from adoptively transferred recipients 72 h after injection of OvaP alone or in combination with TLR agonists.…”

Section: Present Presumably Because Cells Had Not Yet Reached These mentioning

confidence: 99%

“…Superantigen-induced T cell activation and death have previously been associated with decreased Bcl-2 expression and reactive oxygen-dependent changes in transcriptional activity [9,11,18,19]. Activated T cell death has also been reported to require the proapoptotic factors Bim [18,20] and Bax/Bak [21] after treatment with superantigen.…”

Section: Introductionmentioning

confidence: 99%

“…Activated T cell death has also been reported to require the proapoptotic factors Bim [18,20] and Bax/Bak [21] after treatment with superantigen. Mechanisms of activated T cell death during proliferation in the DO11.10 model were tested here by flow cytometric analysis of intracellular Bcl-2 and Bcl-x content and immunoblot detection of average levels of Bim in stimulated T cell populations.…”

Section: Introductionmentioning

confidence: 99%

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Peptide-stimulated DO11.10 T cells divide well but accumulate poorly in the absence of TLR agonist treatment

et al. 2005

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Immunological adjuvants increase the clonal burst size of antigen-specific T cell populations by mechanisms that remain incompletely understood. Using the DO11.10 adoptive transfer system to study peptide-stimulated T cell responses, we found that TLR agonist treatment increased the extent of cellular division undergone by responding T cells, but not by enough to explain the net increases in T cell yield that were achieved. Two novel analyses involving CFSE dye dilution analysis were used to characterize the shortfall, both of which were consistent with the idea that DO11.10 T cells are frequently lost during proliferation unless TLR agonists are present. T cell loss during clonal expansion was correlated with decreased levels of Bcl-2, but TLR agonists did not appear to afford protection by restoring levels of Bcl-2 or of cell surface IL-7Ra chain expression. TLR-mediated protection also failed to correlate with increased expression of Bcl-x or decreased expression of pro-apoptotic Bim. Our findings suggest that DO11.10 T cells stimulated by antigenic peptide in vivo divide well, but fail to accumulate efficiently unless TLR agonists are present.

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Activated T Cell Death In Vivo Mediated by Proapoptotic Bcl-2 Family Member Bim

Cited by 514 publications

References 50 publications

Bim controls IL-15 availability and limits engagement of multiple BH3-only proteins

Bim controls IL-15 availability and limits engagement of multiple BH3-only proteins

Regulatory phosphorylation of Bim: sorting out the ERK from the JNK

Peptide-stimulated DO11.10 T cells divide well but accumulate poorly in the absence of TLR agonist treatment

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