Paclitaxel inhibits killing by murine cytotoxic T lymphocytes <i>in vivo</i> but not <i>in vitro</i>

Robinson, Marc; Ronchese, Franca; Miller, John H.; Flamme, Anne Camille La

doi:10.1038/icb.2009.96

Cited by 8 publications

(6 citation statements)

References 37 publications

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“…hi , highly cytotoxic (28,27,26), and produced large amounts of IFN-g and TNF-a when activated in vitro with specific peptide (27). Cells were harvested on day 6, and 5 3 10 6 cells were injected into recipient mice through the lateral tail vein.…”

Section: Culture and Adoptive Transfer Of Ctlmentioning

confidence: 99%

Allergen-Specific CTL Require Perforin Expression To Suppress Allergic Airway Inflammation

Enomoto

Hyde

Joel

et al. 2012

The Journal of Immunology

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Allergen-specific CTL have a protective effect on allergic airway inflammation, a function thought to be mediated by cytokines, especially IFN-γ. However, the contribution of cytotoxic function to this protective effect has not been investigated. We examined the contribution of cytotoxic function to the therapeutic effect of allergen-specific CTL in allergic airway inflammation. We used a murine model of allergic airway inflammation in which mice were sensitized to OVA and then challenged with the same Ag via the intranasal route. CTL were elicited in these mice by immunization with dendritic cells (DC) or by adoptive transfer of in vitro-activated CD8+ T cells. Hallmark features of allergic asthma, such as infiltration of eosinophils in the bronchoalveolar lavage fluid and mucus production, were assessed. Suppression of allergic airway inflammation by allergen-specific CTL was critically dependent on the expression of perforin, a key component of the cytotoxic machinery. Both perforin-sufficient and perforin-deficient allergen-specific CTL were recovered from the lungs of allergen-sensitized mice and upregulated CD69 expression and secreted the cytokines IFN-γ and TNF-α upon intranasal allergen challenge. However, only perforin-sufficient CTL inhibited eosinophil infiltration in the airway, mucus production, and cytokine accumulation in the bronchoalveolar lavage fluid. Treatment with allergen-specific CTL, but not their perforin-deficient counterparts, was also associated with a decrease in the number of DC in the mediastinal lymph node. Our data suggest that the cytotoxic function of allergen-specific CD8+ T cells is critical to their ability to moderate allergic airway inflammation.

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Section: Culture and Adoptive Transfer Of Ctlmentioning

confidence: 99%

Allergen-Specific CTL Require Perforin Expression To Suppress Allergic Airway Inflammation

Enomoto

Hyde

Joel

et al. 2012

The Journal of Immunology

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“…OVA-expressing (EG7) and non-transfected control cells (EL4) were seeded at 2 × 10 4 cells per well and co-cultured with CTLs (1 × 10 5 ) and control or RA treated monocytes (2 × 10 4 ) for 6–18 hours [73,78]. The MTT assay (Sigma-Aldrich) was used to determine quantity of live cells.…”

Section: Methodsmentioning

confidence: 99%

Continuous retinoic acid induces the differentiation of mature regulatory monocytes but fails to induce regulatory dendritic cells

et al. 2014

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BackgroundMyeloid cells (MC) have potent immunoregulatory abilities that can be therapeutically useful to treat inflammatory disease. However, the factors which promote regulatory myeloid cell differentiation remain poorly understood. We have previously shown that estriol (E3) induces mature regulatory dendritic cells in vivo. To determine whether additional steroid hormones could induce mature regulatory myeloid cells, we investigated the effects of retinoic acid (RA) on MCs. Retinoic acid is a steroid hormone important in regulating mucosal immunity in the gut and promoting myeloid differentiation. We hypothesized that the presence of RA during differentiation would promote the formation of mature regulatory myeloid cells (MCregs).MethodsTo determine RA’s ability to induce regulatory myeloid cells, we differentiated bone marrow progenitor cells with granulocytic-macrophage colony-stimulating factor (GM-CSF) under the influence of RA. We found that day 7 MCs differentiated in the presence of RA had an increase in the percent positive and relative expression levels of both maturation (CD80, CD86, and MHCII) and inhibitory (PD-L1 and PD-L2) markers compared to control cells. Functionally, these day 7 RA MCs expressed increased intracellular IL-10, induced regulatory T cells in vitro compared to controls and suppressed the proliferation of responder immune cells even after inflammatory challenge with LPS.ConclusionRA induced mature regulatory myeloid cells that were suppressive and had a CD11b+ CD11c-Ly6C low/intermediate monocyte phenotype. Surprisingly, RA CD11c+ dendritic cells were not suppressive and could contribute to enhanced proliferation. These results suggest that continuous RA has unique effects on different myeloid populations during monopoeisis and dendropoiesis and promotes a population of regulatory monocytes.

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“…OT-I T cells were activated in vitro by culturing with DC and 0.1 µM SIINFEKL for 4 days, and expanded in 100 U/ml IL-2 for a further 2 days as described [50]. Greater than 95% of the resulting T cells were Vα2 + Vβ5.1/5.2 + and CD8 + CD62L lo CD44 hi .…”

Section: Methodsmentioning

confidence: 99%

Murine CD4+ T Cell Responses Are Inhibited by Cytotoxic T Cell-Mediated Killing of Dendritic Cells and Are Restored by Antigen Transfer

et al. 2012

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Cytotoxic T lymphocytes (CTL) provide protection against pathogens and tumors. In addition, experiments in mouse models have shown that CTL can also kill antigen-presenting dendritic cells (DC), reducing their ability to activate primary and secondary CD8+ T cell responses. In contrast, the effects of CTL-mediated killing on CD4+ T cell responses have not been fully investigated. Here we use adoptive transfer of TCR transgenic T cells and DC immunization to show that specific CTL significantly inhibited CD4+ T cell proliferation induced by DC loaded with peptide or low concentrations of protein antigen. In contrast, CTL had little effect on CD4+ T cell proliferation induced by DC loaded with high protein concentrations or expressing antigen endogenously, even if these DC were efficiently killed and failed to accumulate in the lymph node (LN). Residual CD4+ T cell proliferation was due to the transfer of antigen from carrier DC to host APC, and predominantly involved skin DC populations. Importantly, the proliferating CD4+ T cells also developed into IFN-γ producing memory cells, a property normally requiring direct presentation by activated DC. Thus, CTL-mediated DC killing can inhibit CD4+ T cell proliferation, with the extent of inhibition being determined by the form and amount of antigen used to load DC. In the presence of high antigen concentrations, antigen transfer to host DC enables the generation of CD4+ T cell responses regardless of DC killing, and suggests mechanisms whereby CD4+ T cell responses can be amplified.

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Paclitaxel inhibits killing by murine cytotoxic T lymphocytes in vivo but not in vitro

Cited by 8 publications

References 37 publications

Allergen-Specific CTL Require Perforin Expression To Suppress Allergic Airway Inflammation

Allergen-Specific CTL Require Perforin Expression To Suppress Allergic Airway Inflammation

Continuous retinoic acid induces the differentiation of mature regulatory monocytes but fails to induce regulatory dendritic cells

Murine CD4+ T Cell Responses Are Inhibited by Cytotoxic T Cell-Mediated Killing of Dendritic Cells and Are Restored by Antigen Transfer

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