Suppression of cell-mediated and humoral immune responses by an interleukin-2-immunoglobulin fusion protein in mice.

Kunzendorf, Ulrich; Pohl, Thomas; Bulfone–Paus∥, Silvia; Krause, Hans; Notter, Michael; Onu, Adrian; Walz, Gerd; Diamantstein, T

doi:10.1172/jci118534

Cited by 28 publications

(59 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Administration of IL-2-IgG2b led to suppression of cellular and humoral immune responses [12,14] and had beneficial effects on organ transplantation [13] as well as experimental colitis [15]. However, the transfer of suppression by a fixed number of purified Treg from pIL-2-but not from control plasmid-treated mice showed that the suppression is the result of activated Treg suppressor function and not merely due to their increase in number.…”

Section: Discussionmentioning

confidence: 99%

“…BALB/c mice were injected once or twice intraperitoneally with 10 lg of IL-2-IgG2b fusion protein (a kind gift from Prof. Dr. Bulfone-Paus; see [12]) in PBS, PBS alone or mIgG2b (Sigma) as isotype control. Twenty-four hours after IL-2-IgG2b administration or 36 h after second IL-2 treatment either draining lymph nodes and spleen were analyzed for CD25 and FoxP3 expression, or CD4 + CD25…”

Section: Il-2-igg2b Fusion Protein Treatmentmentioning

confidence: 99%

“…IL-2-and IL-2 receptor-deficient mice die early from T cell hyperactivation [8][9][10][11]. Treatment of wild-type mice with an IL-2-IgG fusion protein (IL-2-IgG2b) suppresses cell-mediated and humoral immune responses in mice [12][13][14] and protects mice from TNBS-induced colitis [15]. The suppressive effects of IL-2 are attributed to its important role for the survival and expansion of Treg in the periphery [6, [16][17][18].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

IL‐2 induces in vivo suppression by CD4⁺CD25⁺Foxp3⁺ regulatory T cells

et al. 2008

View full text Add to dashboard Cite

Interleukin-2 (IL-2) treatment is currently used to enhance T cell-mediated immune responses against tumors or in viral infections. At the same time, IL-2 is essential for the peripheral homeostasis of CD4 + CD25 + Foxp3 + regulatory T cells (Treg). In our study, weshow that IL-2 is also an important activator of Treg suppressive activity in vivo. IL-2 treatment induces Treg expansion as well as IL-10 production and increases their suppressive potential in vitro. Importantly, in vivo application of IL-2 via gene-gun vaccination using IL-2 encoding DNA plasmids (pIL-2) inhibited naive antigen-specific T cell proliferation as well as a Th1-induced delayed type hypersensitivity response. The suppressive effect can be transferred onto naive animals by Treg from IL-2-treated mice and the suppression depends on the synergistic action of IL-10 and TGF-b. These data highlight that during therapeutic treatment with IL-2 the concomitant activation of Treg may indeed counteract the intended activation of cellular immunity.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Il-2-igg2b Fusion Protein Treatmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

IL‐2 induces in vivo suppression by CD4⁺CD25⁺Foxp3⁺ regulatory T cells

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Interestingly, IL-2-IgG2b administration suppressed cellular and humoral responses [34,36,38] as well as an experimental model of colitis [37] and organ transplantation [35]. The suppression was not due to depletion of IL-2-binding cells such as activated T cells; rather, the frequency of CD25 + T cells was increased.…”

Section: Does Il-2 Activate In Vivo Suppression and What Is The Supprmentioning

confidence: 99%

“…In a series of papers dating back to 1996, the effect of in vivo administration of an agonistic IL-2-IgG2b fusion protein on adaptive immunity was analyzed [34][35][36][37][38]. Interestingly, IL-2-IgG2b administration suppressed cellular and humoral responses [34,36,38] as well as an experimental model of colitis [37] and organ transplantation [35].…”

Section: Does Il-2 Activate In Vivo Suppression and What Is The Supprmentioning

confidence: 99%

Regulation of CD4⁺CD25⁺ regulatory T cell activity: it takes (IL‐)two to tango

2005

View full text Add to dashboard Cite

Although CD4 + CD25 + regulatory T cells (Treg) represent a well-characterized population of T cells with in vitro and in vivo suppressive capacity, the basic mechanisms of suppression are still not understood. The constitutive expression of the high-affinity receptor for IL-2 has raised the question about the role of IL-2 in Treg function. Here, we review recent data indicating that IL-2 is not only necessary for the homeostasis of Treg but is also critical for the activation of Treg function. Since Treg do not produce IL-2 by themselves, their capacity to utilize IL-2 secreted by other T cells appears to be an essential component of Treg biology. This indicates that Treg suppressive activity is controlled by interaction with activated target cells via the soluble mediator IL-2. In Treg, IL-2 has been identified as a potent inducer of the immunosuppressive cytokine IL-10, an important mediator of Treg suppression in vivo. The efficient capture of IL-2 by Treg may, under conditions of limited IL-2 supply, cause IL-2 deprivation of responder T cells. This competition can explain some of the currently discussed discrepancies between in vivo and in vitro activity of Treg.

show abstract

IL-15-IgG2b fusion protein accelerates and enhances a Th2 but not a Th1 immune responsein vivo, while IL-2-IgG2b fusion protein inhibits both

et al. 1998

View full text Add to dashboard Cite

We have explored how IL-15 influences Th1 or Th2 type immune response in vivo. Intraperitoneal application of an IL-15-IgG2b fusion protein (FP) to mice did neither significantly affect the footpad swelling nor the production of hemagglutinizing antibodies in a delayed type hypersensitivity reaction to sheep red blood cells. In contrast, in an established murine Th2 model of sensitization to ovalbumin (OVA), IL-15-IgG2b FP plus OVA sensitization resulted in massively accelerated and enhanced allergen-specific IgE and IgG1 antibody production. In vitro, stimulation of spleen cells from OVA-sensitized mice with OVA+IL-15 or OVA+IL-15-IgG2b resulted in a significantly enhanced IgE production. IL-4 secretion was significantly induced by IL-15 but not by IL-15-IgG2b. An IL-2-IgG2b FP with the same Fc tail as the IL-15-IgG2b FP was used as control in both models. In striking contrast to the IL-15-IgG2b FP, IL-2-IgG2b significantly inhibited the Th2 type antibody production in vivo. The current study suggests that IL-15-IgG2b may be employed as a potent accelerator and enhancer of Th2 type immune responses in vivo, while IL-2-IgG2b can suppress the latter.

show abstract

Suppression of cell-mediated and humoral immune responses by an interleukin-2-immunoglobulin fusion protein in mice.

Cited by 28 publications

References 29 publications

IL‐2 induces in vivo suppression by CD4⁺CD25⁺Foxp3⁺ regulatory T cells

IL‐2 induces in vivo suppression by CD4⁺CD25⁺Foxp3⁺ regulatory T cells

Regulation of CD4⁺CD25⁺ regulatory T cell activity: it takes (IL‐)two to tango

IL-15-IgG2b fusion protein accelerates and enhances a Th2 but not a Th1 immune responsein vivo, while IL-2-IgG2b fusion protein inhibits both

Contact Info

Product

Resources

About

Suppression of cell-mediated and humoral immune responses by an interleukin-2-immunoglobulin fusion protein in mice.

Cited by 28 publications

References 29 publications

IL‐2 induces in vivo suppression by CD4+CD25+Foxp3+ regulatory T cells

IL‐2 induces in vivo suppression by CD4+CD25+Foxp3+ regulatory T cells

Regulation of CD4+CD25+ regulatory T cell activity: it takes (IL‐)two to tango

IL-15-IgG2b fusion protein accelerates and enhances a Th2 but not a Th1 immune responsein vivo, while IL-2-IgG2b fusion protein inhibits both

Contact Info

Product

Resources

About

IL‐2 induces in vivo suppression by CD4⁺CD25⁺Foxp3⁺ regulatory T cells

IL‐2 induces in vivo suppression by CD4⁺CD25⁺Foxp3⁺ regulatory T cells

Regulation of CD4⁺CD25⁺ regulatory T cell activity: it takes (IL‐)two to tango