A Soluble Lymphocyte Activation Gene-3 Molecule Used as a Vaccine Adjuvant Elicits Greater Humoral and Cellular Immune Responses to Both Particulate and Soluble Antigens

mir, Samir El; Triebel, Frédéric

doi:10.4049/jimmunol.164.11.5583

Cited by 64 publications

(38 citation statements)

References 22 publications

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“…Finally we showed that LAG-3-transfected tumors in syngeneic mice completely regressed, or their growth was markedly reduced, which was in contrast to the aggressive growth of untransfected cells (30). We also showed that murine LAG-3Ig acts as an adjuvant for Th1 responses and cytotoxic T cell responses to proteinaceous Ags (31). Because murine T cells do not express class II, it seems likely that these responses are induced via a direct effect of LAG-3Ig on class II ϩ APC.…”

Section: Stimulation Of Cd8mentioning

confidence: 79%

“…In previous studies LAG-3Ig was found to act as a vaccine adjuvant for the induction of T cell responses to nominal Ag in mice and to induce in vitro cytokine production by monocyte-derived human DC (31,36). To further analyze the role of LAG-3, monocyte-derived human DC cultured with IL-4 and GM-CSF for 6 days were incubated with soluble LAG-3Ig.…”

Section: Lag-3 Induces Morphological Changes In Immature DCmentioning

confidence: 99%

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Maturation and Activation of Dendritic Cells Induced by Lymphocyte Activation Gene-3 (CD223)

Andreae

Piras²,

Burdin³

et al. 2002

The Journal of Immunology

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158

139

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Lymphocyte activation gene-3 (LAG-3) is an MHC class II ligand expressed on activated T and NK cells. A LAG-3Ig fusion protein has been used in mice as an adjuvant protein to induce antitumor responses and specific CD8 and CD4 Th1 responses to nominal Ags. In this work we report on the effect of LAG-3Ig on the maturation and activation of human monocyte-derived dendritic cells (DC). LAG-3Ig binds MHC class II molecules expressed in plasma membrane lipid rafts on immature human DC and induces rapid morphological changes, including the formation of dendritic projections. LAG-3Ig markedly up-regulates the expression of costimulatory molecules and the production of IL-12 and TNF-α. Consistent with this effect on DC maturation, LAG-3Ig disables DC in their capacity to capture soluble Ags. These events are associated with the acquisition of professional APC function, because LAG-3Ig increases the capacity of DC to stimulate the proliferation and IFN-γ response by allogeneic T cells. These effects were not observed when using ligation of MHC class II by specific mAb. Class II-mediated signals induced by a natural ligand, LAG-3, lead to complete maturation of DC, which acquire the capacity to trigger naive T cells and drive polarized Th1 responses.

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Section: Stimulation Of Cd8mentioning

confidence: 79%

Section: Lag-3 Induces Morphological Changes In Immature DCmentioning

confidence: 99%

Maturation and Activation of Dendritic Cells Induced by Lymphocyte Activation Gene-3 (CD223)

Andreae

Piras²,

Burdin³

et al. 2002

The Journal of Immunology

Self Cite

158

139

View full text Add to dashboard Cite

show abstract

“…A soluble murine LAG-3-Ig fusion protein induced MHC class II mediated signaling in DC, leading to their activation and/or maturation as well as production of cytokines [19][20][21][22]. In addition, mLAG-3-Ig was shown to reduce tumor growth [23,24] and to increase CD8 cytotoxic responses and CD4 Th1 responses in mice [25].…”

Section: Introductionmentioning

confidence: 99%

Expression of lymphocyte activation gene 3 (LAG-3) on B cells is induced by T cells

Kisielow¹,

Kisielow²,

et al. 2005

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Lymphocyte activation gene 3 (LAG-3/CD223) is a CD4 homolog known to be selectively expressed in activated T and NK cells. It is thought to have a negative regulatory function in T cells. With the help of new monoclonal antibodies against mouse LAG-3, we show that LAG-3 surface expression is not limited to activated T and NK cells but is also found on activated B cells. Induction of B cell surface expression is T cell dependent and mediated by a soluble factor. The majority of LAG-3 on B cell surface is endogenously produced, even though soluble LAG-3 is present in the culture supernatants and can be passively absorbed. As B cells express LAG-3 in a T cell dependent manner and not when activated by Toll-like-receptor agonists alone, we propose LAG-3 as a new marker of T cell induced B cell activation.

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“…ϩ Th cells and the cross-priming of CD8 ϩ CTLs (2,3,8). In mice, tumor rejection induced by LAG-3 was associated with induction of tumor-specific CD8 cells (9,10) and presence of CD86-expressing APCs, NK cells, granulocytes, and infiltrating T cells as well as production of IFN-␥, CCL2/MCP-1, and CCL5/RANTES at the tumor site (11).…”

mentioning

confidence: 99%

A Soluble Form of Lymphocyte Activation Gene-3 (IMP321) Induces Activation of a Large Range of Human Effector Cytotoxic Cells

Brignone

Grygar

Marcu

et al. 2007

The Journal of Immunology

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The principal antitumor immune response is mediated through the activation of type 1 cytotoxic (Tc1) CD8 T cells, NK cells, and monocytes/macrophages. In this study, we investigated the potency of a clinical-grade soluble form of lymphocyte activation gene-3 protein (IMP321), a physiological high-affinity MHC class II binder, at inducing in PBMCs an appropriate cytotoxic-type response in short-term ex vivo assays. We found that IMP321 binds to a minority (<10%) of MHC class II + cells in PBMCs, including all myeloid dendritic cells, and a small fraction of monocytes. Four hours after addition of IMP321 to PBMCs, these myeloid cells produce TNF-α and CCL4 as determined by intracellular staining. At 18 h, 1% of CD8+ T cells and 3.7% NK cells produce Tc1 cytokines such as IFN-γ and/or TNF-α (mean values from 60 blood donors). Similar induction was observed in metastatic cancer patient PBMCs, but the values were lower for the NK cell subset. Early APC activation by IMP321 is needed for this Tc1-type activation because pure sorted CD8+ T cells could not be activated by IMP321. Only Ag-experienced, fully differentiated granzyme+ CD8 T cells (effector and effector memory but not naive or central memory T cells) are induced by IMP321 to full Tc1 activation. In contrast to IMP321, TLR1-9 agonists induce IL-10 and are therefore unable to induce this Tc1 IFN-γ+ response. Thus, IMP321 has many properties that confirm its potential to be a new class of immunopotentiator in cancer patients.

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A Soluble Lymphocyte Activation Gene-3 Molecule Used as a Vaccine Adjuvant Elicits Greater Humoral and Cellular Immune Responses to Both Particulate and Soluble Antigens

Cited by 64 publications

References 22 publications

Maturation and Activation of Dendritic Cells Induced by Lymphocyte Activation Gene-3 (CD223)

Maturation and Activation of Dendritic Cells Induced by Lymphocyte Activation Gene-3 (CD223)

Expression of lymphocyte activation gene 3 (LAG-3) on B cells is induced by T cells

A Soluble Form of Lymphocyte Activation Gene-3 (IMP321) Induces Activation of a Large Range of Human Effector Cytotoxic Cells

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