Dendritic cells and macrophages are required for Th1 development of CD4+ T cells from αβ TCR transgenic mice: IL-12 substitution for macrophages to stimulate IFN-γ production is IFN-γ-dependent

Macatonia, Steven E.; Hsieh, Chyi-Song; Murphy, Kenneth M.; O’Garra, Anne

doi:10.1093/intimm/5.9.1119

Cited by 315 publications

(146 citation statements)

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“…Current data suggest that protection to Leishmania infection requires the effective activation of several cell populations, including DC, Ag-specific CD4 ϩ and CD8 ϩ T cells, and macrophages (8,51,60). Resistance to leishmaniasis has been associated with a predominant IL-12 and IFN-␥ production from the Ag-specific CD4 ϩ Th lymphocyte population termed as Th1 immune response (61,62). These cells along with CD8 ϩ T cytotoxic lymphocytes are then effective in promoting macrophage activation, and the intracellular Leishmania are killed in a NO-dependent manner (63)(64)(65).…”

Section: Discussionmentioning

confidence: 99%

Ubiquitin Conjugation of Open Reading Frame F DNA Vaccine Leads to Enhanced Cell-Mediated Immune Response and Induces Protection against Both Antimony-Susceptible and -Resistant Strains ofLeishmania donovani

Sharma

Madhubala

2009

The Journal of Immunology

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Resistance of Leishmania donovani to sodium antimony gluconate has become a critical issue in the current, prolonged epidemic in India. Hence, there is an urgent need for a vaccine that is protective against both antimony-susceptible and -resistant strains of L. donovani. The multigene LD1 locus located on chromosome 35 of Leishmania is amplified in ∼15% of the isolates examined. The open reading frame F (ORFF), a potential vaccine candidate against visceral leishmaniasis, is part of the multigene LD1 locus. ORFF was expressed as a chimeric conjugate of ubiquitin to elicit an Ag-specific cell-mediated immune response. Analysis of the cellular immune responses of ubiquitin-conjugated ORFF (UBQ-ORFF) DNA-immunized, uninfected BALB/c mice demonstrated that the vaccine induced enhanced IFN-γ-producing CD4+ and CD8+ T cells compared with nonubiquitinated ORFF DNA vaccine. Higher levels of IL-12 and IFN-γ and the low levels of IL-4 and IL-10 further indicated that the immune responses with UBQ-ORFF were mediated toward the Th1 rather than Th2 type. Infection of immunized mice with either the antimony-susceptible (AG83) or -resistant (GE1F8R) L. donovani strain showed that UBQ-ORFF DNA vaccine induced higher protection when compared with ORFF DNA. UBQ-ORFF DNA-immunized and -infected mice showed a significant increase in IL-12 and IFN-γ and significant down-regulation of IL-10. High levels of production of nitrite and superoxide, two macrophage-derived oxidants that are critical in controlling Leishmania infection, were observed in protected mice. The feasibility of using ubiquitinated-conjugated ORFF DNA vaccine as a promising immune enhancer for vaccination against both antimony-susceptible and -resistant strains of L. donovani is reported.

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Section: Discussionmentioning

confidence: 99%

Ubiquitin Conjugation of Open Reading Frame F DNA Vaccine Leads to Enhanced Cell-Mediated Immune Response and Induces Protection against Both Antimony-Susceptible and -Resistant Strains ofLeishmania donovani

Sharma

Madhubala

2009

The Journal of Immunology

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“…The differentiation of Th1 cells reactive to luminal Ag is dependent on both the cognate interaction between naive T cells and APCs and the stimulatory effects of cytokines such as IL-12 (31). This effect of APC-derived IL-12 is enhanced by the IFN-␥ release from the developing Th1 lymphocyte (32). In the intact gastrointestinal tract, Ag presentation also results in IL-10 release that acts to antagonize the positive feedback loop toward Th1 lymphocyte differentiation.…”

Section: Discussionmentioning

confidence: 99%

The Prevention and Treatment of Murine Colitis Using Gene Therapy with Adenoviral Vectors Encoding IL-10

Lindsay

Ciesielski

Scheinin

et al. 2001

The Journal of Immunology

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IL-10-deficient (IL-10−/−) mice develop colitis with many similarities to Crohn’s disease. Daily IL-10 injections have a short systemic half-life and are unable to induce complete remission in IL-10−/− mice with established disease. In this paper, we investigate the duration, potency, and immunogenicity of gene therapy using an adenoviral vector encoding murine IL-10 (AdvmuIL-10). A single systemic injection of AdvmuIL-10 was sufficient not only to prevent the onset of colitis for at least 10 wk but also to induce clinical and histological remission in mice with established disease. In addition, AdvmuIL-10 diminished the systemic manifestations of disease, including elevated acute-phase proteins, as well as the local consequences of inflammation such as raised stool IL-1β concentrations. Both IL-10 protein and the effects of secreted IL-10 were detectable for 10 wk after AdvmuIL-10 injection. Furthermore, the immunoregulatory effect of a single AdvmuIL-10 injection was manifest both by a reduction in TNF-α, IFN-γ, and RANTES release from stimulated splenocyte cultures, and also by a change in the proportion of CD45RBhigh/low lymphocytes in the spleen compared with control mice. The delivery of AdvmuIL-10 resulted in a significantly diminished host antiadenoviral response compared with control adenoviral vectors. Thus, gene therapy strategies using adenoviral vectors encoding immunoregulatory and antiinflammatory cytokines may prove to be a potent approach for the treatment of chronic inflammatory disease. Antiinflammatory cytokine expression protects against immune responses directed at gene vectors.

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“…+ cells, cells were cultured at 0.5 Â 10 6 /ml in the presence of irradiated APC (0.5 Â 10 5 /ml) enriched for dendritic cells 44 in ex vivo medium (Biowhitaker, MA, USA), supplemented with 4.8 mM L-glutamine, 1 mM sodium pyruvate, 1 Â non essential amino acids, 5 Â 10 À5 M b2-mercaptoethanol, 400 U/ml penicillin, 0.24 mg/ml streptomycin sulfate and 5% heats inactivated FCS.…”

Section: Cell Culturementioning

confidence: 99%

A1/Bfl-1 expression is restricted to TCR engagement in T lymphocytes

et al. 2003

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We analyzed regulation of the prosurvival Bcl-2 homologue A1, following T-cell receptor (TCR) or cytokine receptor engagement. Activation of CD4 + or CD8 + T cells by antigenic peptides induced an early but transient IL-2-independent expression of A1 and Bcl-xl mRNA and proteins, whereas expression of Bcl-2 was delayed and required IL-2. Cytokines such as IL-2, IL-4, IL-7 or IL-15 prevented apoptosis of activated T cells that effect being associated with the maintenance of Bcl-2, but not of A1 expression. However, restimulation of activated or posteffector T cells with antigenic peptide strongly upregulated A1 mRNA and maintained A1 protein expression. IL-4, IL-7 or IL-15 also prevented cell death of naive T cells. In those cells, cytokines upregulated Bcl-2, but not A1 expression. Therefore, in naive, activated and posteffector T cells, expression of A1 is dependent on TCR but not on cytokine receptor engagement, indicating that A1 is differently regulated from Bcl-xl and Bcl-2.

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Dendritic cells and macrophages are required for Th1 development of CD4⁺ T cells from αβ TCR transgenic mice: IL-12 substitution for macrophages to stimulate IFN-_γ production is IFN-_γ-dependent

Cited by 315 publications

References 0 publications

Ubiquitin Conjugation of Open Reading Frame F DNA Vaccine Leads to Enhanced Cell-Mediated Immune Response and Induces Protection against Both Antimony-Susceptible and -Resistant Strains ofLeishmania donovani

Ubiquitin Conjugation of Open Reading Frame F DNA Vaccine Leads to Enhanced Cell-Mediated Immune Response and Induces Protection against Both Antimony-Susceptible and -Resistant Strains ofLeishmania donovani

The Prevention and Treatment of Murine Colitis Using Gene Therapy with Adenoviral Vectors Encoding IL-10

A1/Bfl-1 expression is restricted to TCR engagement in T lymphocytes

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