High antigen dose and activated dendritic cells enable Th cells to escape regulatory T cell‐mediated suppression <i>in vitro</i>

George, Thaddeus C.; Bilsborough, Janine; Viney, Joanne L.; Norment, Anne M.

doi:10.1002/immu.200310026

Cited by 81 publications

(87 citation statements)

References 32 publications

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“…ϩ T cells in vitro (12,18). Therefore, the reversal of suppression seen with anti-CD28 in vitro may be secondary to the potent effects of anti-CD28-mediated costimulation on the induction of endogenous IL-2 production.…”

Section: Cd25mentioning

confidence: 99%

Cutting Edge: IL-2 Is Critically Required for the In Vitro Activation of CD4+CD25+ T Cell Suppressor Function

Thornton

Donovan

Piccirillo

et al. 2004

The Journal of Immunology

491

388

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CD4+CD25+ T cells are potent immunoregulatory cells that suppress TCR-induced proliferation of CD4 and CD8 T cells in vitro by a cell contact-dependent mechanism. Addition of IL-2 or anti-CD28 abrogates CD4+CD25+-mediated suppression of proliferation and has been assumed to “break suppression.” We examined IL-2 mRNA by quantitative PCR in cocultures of mouse CD4+CD25+ and CD4+CD25− T cells. Although IL-2 gene transcription was inhibited in the presence or absence of exogenous IL-2, the addition of anti-CD28 stimulated endogenous IL-2 production. Surprisingly, transcription of IL-2 mRNA was also restored in the cocultures in the presence of anti-IL-2. These results are most compatible with a model in which CD4+CD25+ T cells do not suppress the initial activation of CD4+CD25− T cells, but mediate their suppressive effects following production of IL-2 by the responder cells resulting in both the expansion of the CD4+CD25+ T cells and the induction of their suppressor function.

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Section: Cd25mentioning

confidence: 99%

Cutting Edge: IL-2 Is Critically Required for the In Vitro Activation of CD4+CD25+ T Cell Suppressor Function

Thornton

Donovan

Piccirillo

et al. 2004

The Journal of Immunology

491

388

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“…Such activity is generally limited toward weakly, but not strongly, stimulated T cells (33)(34)(35)(36), with physiological implication that it might function primarily to raise the threshold of autoimmune reactions (35). Having established the augmenting effect of 4-1BB costimulation on cell proliferation, we sought to determine whether the CD4 ϩ CD25 ϩ T cells remained suppressive after proliferation.…”

Section: Cells Remained Suppressive After 4-1bb-augmented Proliferationmentioning

confidence: 99%

The 4-1BB Costimulation Augments the Proliferation of CD4+CD25+ Regulatory T Cells

Zheng

Wang

Chen

2004

The Journal of Immunology

140

113

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The thymus-derived CD4+CD25+ T cells belong to a subset of regulatory T cells potentially capable of suppressing the proliferation of pathogenic effector T cells. Intriguingly, these suppressor cells are themselves anergic, proliferating poorly to mitogenic stimulation in culture. In this study, we find that the 4-1BB costimulator receptor, best known for promoting the proliferation and survival of CD8+ T cells, also induces the proliferation of the CD4+CD25+ regulatory T cells both in culture and in vivo. The proliferating CD4+CD25+ T cells produce no detectable IL-2, suggesting that 4-1BB costimulation of these cells does not involve IL-2 production. The 4-1BB-expanded CD4+CD25+ T cells are functional, as they remain suppressive to other T cells in coculture. These results support the notion that the peripheral expansion of the CD4+CD25+ T cells is controlled in part by costimulation.

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“…One possible explanation for the discrepancy of the in vitro vs. in vivo effects of PD-L2-Fc is that PD-L2-Fc might inhibit Treg function. To examine this possibility, we tested the role of PD-L2-Fc on proliferation and cytokine production by Th2 cells in the presence of Treg using the system described by George et al [33]. By flow cytometric analysis, PD-1 was expressed on the majority of CD4 + CD25 + Treg (Fig.…”

Section: Pd-l2-fc Does Not Interfere With the Suppressor Activity Of mentioning

confidence: 99%

Paradoxical role of programmed death‐1 ligand 2 in Th2 immune responses in vitro and in a mouse asthma model in vivo

et al. 2004

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Programmed death-1 ligand 2 (PD-L2) is a ligand for programmed death-1 (PD-1), a receptor that plays an inhibitory role in T cell activation. Since previous studies have shown upregulation of PD-L2 expression by Th2 cytokines, and asthma is driven by a Th2 response, we hypothesized that PD-L2 might be involved in regulation of the immune response in this disease. We have found that lungs from asthmatic mice had sustained up-regulation of PD-1 and PD-L2, with PD-L2 primarily on dendritic cells. Although addition of PD-L2-Fc in vitro led to decreased T cell proliferation and cytokine production, administration of PD-L2-Fc in vivo in a mouse asthma model resulted in elevated serum IgE levels, increased eosinophilic and lymphocytic infiltration into bronchoalveolar lavage fluid, higher number of cells in the draining lymph nodes, and production of IL-5 and IL-13 from these cells. Although PD-1 was expressed on regulatory T cells, PD-L2-Fc did not affect regulatory T cell activity in vitro. This study provides in vivo evidence of an exacerbated inflammatory response following PD-L2-Fc administration and indicates a potential role for this molecule in Th2-mediated diseases such as asthma.

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High antigen dose and activated dendritic cells enable Th cells to escape regulatory T cell‐mediated suppression in vitro

Cited by 81 publications

References 32 publications

Cutting Edge: IL-2 Is Critically Required for the In Vitro Activation of CD4+CD25+ T Cell Suppressor Function

Cutting Edge: IL-2 Is Critically Required for the In Vitro Activation of CD4+CD25+ T Cell Suppressor Function

The 4-1BB Costimulation Augments the Proliferation of CD4+CD25+ Regulatory T Cells

Paradoxical role of programmed death‐1 ligand 2 in Th2 immune responses in vitro and in a mouse asthma model in vivo

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