Irradiation up‐regulates CD80 expression through two different mechanisms in spleen B cells, B lymphoma cells, and dendritic cells

Torihata, Hideko; Ishikawa, Fumio; Okada, Yayoi; Tanaka, Yuriko; Uchida, Tetsuya; Suguro, Toru; Kakiuchi, Terutaka

doi:10.1111/j.1365-2567.2004.01872.x

Cited by 23 publications

(15 citation statements)

References 51 publications

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“…These authors found that localized ionizing irradiation enhanced the generation of endogenous antigen-specific T CD8 , which corresponded with increased levels of antigen within the draining lymph node. This finding is consistent with studies showing that irradiation induces upregulation of co-stimulatory molecule expression on APCs, including DCs, leading to enhanced T cell stimulatory capacity in vitro (70, 71). In the SV11 model, irradiation was not required to trigger T CD8 against the endogenous T Ag, as TCR-IV T CD8 in both the spleen and the CLN proliferated following adoptive transfer.…”

Section: Discussionsupporting

confidence: 92%

CD8+ T Cells Targeting a Single Immunodominant Epitope are Sufficient for Elimination of Established SV40 T Antigen-Induced Brain Tumors

Tatum

Mylin

Bender

et al. 2008

The Journal of Immunology

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Immunotherapy of established solid tumors is rarely achieved, and the mechanisms leading to success remain to be elucidated. We previously showed that extended control of advanced-stage autochthonous brain tumors is achieved following adoptive transfer of naive C57BL/6 splenocytes into sublethally irradiated line SV11 mice expressing the SV40 T Ag (T Ag) oncoprotein, and was associated with in vivo priming of CD8+ T cells (TCD8) specific for the dominant epitope IV (T Ag residues 404–411). Using donor lymphocytes derived from mice that are tolerant to epitope IV or a newly characterized transgenic mouse line expressing an epitope IV-specific TCR, we show that epitope IV-specific TCD8 are a necessary component of the donor pool and that purified naive epitope IV-specific TCD8 are sufficient to promote complete and rapid regression of established tumors. While transfer of naive TCR-IV cells alone induced some initial tumor regression, increased survival of tumor-bearing mice required prior conditioning of the host with a sublethal dose of gamma irradiation and was associated with complete tumor eradication. Regression of established tumors was associated with rapid accumulation of TCR-IV T cells within the brain following initial priming against the endogenous T Ag in the peripheral lymphoid organs. Additionally, persistence of functional TCR-IV cells in both the brain and peripheral lymphoid organs was associated with long-term tumor-free survival. Finally, we show that production of IFN-γ, but not perforin or TNF-α, by the donor lymphocytes is critical for control of autochthonous brain tumors.

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Section: Discussionsupporting

confidence: 92%

CD8+ T Cells Targeting a Single Immunodominant Epitope are Sufficient for Elimination of Established SV40 T Antigen-Induced Brain Tumors

Tatum

Mylin

Bender

et al. 2008

The Journal of Immunology

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“…2 A ). Indeed, previous reports, including ours, have demonstrated a rapid activation of DCs at the lymphopenic phase after chemotherapy and TBI, associating with significant increases in the Ag-specific responses of adoptively transferred T cells (3, 14, 18, 19, 48, 49). Paulos et al demonstrated that this rapid DC activation is attributed to the significant damage to the integrity of mucosal barriers and translocation of bacterial products (LPS; a TLR4 ligand) (3).…”

Section: Discussionsupporting

confidence: 52%

Recovery from Cyclophosphamide-Induced Lymphopenia Results in Expansion of Immature Dendritic Cells Which Can Mediate Enhanced Prime-Boost Vaccination Antitumor Responses In Vivo When Stimulated with the TLR3 Agonist Poly(I:C)

Salem

Díaz-Montero

Al-Khami

et al. 2009

The Journal of Immunology

100

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Recent preclinical studies suggest that vaccination following adoptive transfer of CD8+ T cells into a lymphopenic host can augment the therapeutic antitumor responses of the transferred cells. However, the mechanism by which the lymphopenic microenvironment benefits Ag-specific CD8+ T cell responses remains elusive. We show herein that induction of lymphodepletion by a single 4 mg cyclophosphamide (CTX) treatment induces a marked expansion of immature dendritic cells (DCs) in the peripheral blood on days 8–16 post-CTX (termed restoration phase). In vitro, these DCs were functional, because they showed normal phagocytosis and effective Ag presentation capability upon activation. In vivo, administration of the TLR3 agonist poly(I:C) at the peak of DC expansion (day 12 postlymphopenia) induced inflammatory cytokine production and increases in the number of activated DCs in lymph nodes. Importantly, boosting with gp10025–33 melanoma peptide combined with poly(I:C) 12 days after an initial priming with the same regimen significantly increased the expansion and the antitumor efficacy of adoptively transferred pmel-1 CD8+ T cells. These responses were abrogated after depletion of activated DCs during Ag boosting. In conclusion, our data show that CTX treatment induces, during the restoration phase, expansion of immature DCs, which are functional and can be exploited in vivo to foster more effective antitumor adoptive immunotherapy strategies.

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“…Irradiation and/or chemotherapy leads to activation of host cells, resulting in the release of proinflammatory cytokines, such as TNF-α, IL-1 and IL-4 [71][72][73][74], and upregulation of co-stimulatory molecules, such as CD80 [75]. In a recent study, activation markers I-A b (class II) and CD86 were upregulated on splenic DCs as early as 6 h after TBI.…”

Section: Effects Of Lymphodepleting Radiation and Chemotherapy On Apcmentioning

confidence: 99%

Sinks, suppressors and antigen presenters: how lymphodepletion enhances T cell-mediated tumor immunotherapy

Klebanoff

Khong

Antony

et al. 2005

Trends in Immunology

404

288

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Lymphodepletion followed by adoptive cell transfer (ACT) of autologous, tumor-reactive T cells boosts antitumor immunotherapeutic activity in mouse and in humans. In the most recent clinical trials, lymphodepletion together with ACT has an objective response rate of 50% in patients with solid metastatic tumors. The mechanisms underlying this recent advance in cancer immunotherapy are beginning to be elucidated and include: the elimination of cellular cytokine 'sinks' for homeostatic γ C -cytokines, such as interleukin-7 (IL-7), IL-15 and possibly IL-21, which activate and expand tumor-reactive T cells; the impairment of CD4 + CD25 + regulatory T (Treg) cells that suppress tumorreactive T cells; and the induction of tumor apoptosis and necrosis in conjunction with antigenpresenting cell activation. Knowledge of these factors could be exploited therapeutically to improve the in vivo function of adoptively transferred, tumor-reactive T cells for the treatment of cancer.

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Irradiation up‐regulates CD80 expression through two different mechanisms in spleen B cells, B lymphoma cells, and dendritic cells

Cited by 23 publications

References 51 publications

CD8+ T Cells Targeting a Single Immunodominant Epitope are Sufficient for Elimination of Established SV40 T Antigen-Induced Brain Tumors

CD8+ T Cells Targeting a Single Immunodominant Epitope are Sufficient for Elimination of Established SV40 T Antigen-Induced Brain Tumors

Recovery from Cyclophosphamide-Induced Lymphopenia Results in Expansion of Immature Dendritic Cells Which Can Mediate Enhanced Prime-Boost Vaccination Antitumor Responses In Vivo When Stimulated with the TLR3 Agonist Poly(I:C)

Sinks, suppressors and antigen presenters: how lymphodepletion enhances T cell-mediated tumor immunotherapy

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