CTLA-4 expressed by human dendritic cells modulates thei cytokine secretion and induction of T cell proliferation

<p>CTLA-4 is the major nefative regulator of T cell response. We have analyzed the expression of CTLA-4 in human monocytes and monocyte-derived DCs and the effects of its engagement on cytokine production and T cell stimulatory activity by mature DCs (mDCs). We found the CTLA-4 was highly expressed on freshly isolated monocytes, then down-modulated on the immature DCs (iDCs) and upregulated on mDCs. Treatment of mDCS with an agonistic anti-CTLA-4 m Ab enhanced secretion of IL-10 but reduced secretion of IL-8 and IL-12, as well as autologous CD4* T-cell proliferation in response to simulation with PPD recall antigenloaded-DCs. Neutralization of IL-10 with an anti-IL-10 antibody partially restored the ability of anti-CTLA-4-treated mDCs to stimulate T cell proliferation in response to PPD. Our data provide the first evidence that CTLA-4 receptor is expressed by human mDCs and exerts immune modulatory effects in these cells.</p>

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Viral Neuraminidase Treatment of Dendritic Cells Enhances Antigen-Specific CD8+ T Cell Proliferation, but Does Not Account for the CD4+ T Cell Independence of the CD8+ T Cell Response during Influenza Virus Infection

Virology ◽

10.1006/viro.2001.0992 ◽

2001 ◽

Vol 286 (2) ◽

pp. 403-411 ◽

Cited By ~ 11

Author(s):

SangKon Oh ◽

Gabrielle T. Belz ◽

Maryna C. Eichelberger

Keyword(s):

Cell Proliferation ◽

Dendritic Cells ◽

Influenza Virus ◽

T Cell ◽

Influenza Virus Infection ◽

Cd8 T Cell ◽

T Cell Response ◽

Cd4 T Cell ◽

T Cell Proliferation ◽

Neuraminidase Treatment

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Faculty Opinions recommendation of Epidermal and dermal dendritic cells display differential activation and migratory behavior while sharing the ability to stimulate CD4+ T cell proliferation in vivo.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1121863.578941 ◽

2008 ◽

Author(s):

James Campbell

Keyword(s):

Cell Proliferation ◽

Dendritic Cells ◽

T Cell ◽

Cd4 T Cell ◽

T Cell Proliferation ◽

Migratory Behavior ◽

Differential Activation

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HIV inhibits CD4+ T-cell proliferation by inducing indoleamine 2,3-dioxygenase in plasmacytoid dendritic cells

Blood ◽

10.1182/blood-2006-07-034785 ◽

2006 ◽

Vol 109 (8) ◽

pp. 3351-3359 ◽

Cited By ~ 201

Author(s):

Adriano Boasso ◽

Jean-Philippe Herbeuval ◽

Andrew W. Hardy ◽

Stephanie A. Anderson ◽

Matthew J. Dolan ◽

...

Keyword(s):

Cell Proliferation ◽

Dendritic Cells ◽

T Cell ◽

Functional Impairment ◽

Plasmacytoid Dendritic Cells ◽

Cd4 T Cell ◽

T Cell Proliferation ◽

Type I ◽

Indoleamine 2,3 Dioxygenase

AbstractInfection with the human immunodeficiency virus type-1 (HIV) results in acute and progressive numeric loss of CD4+ T-helper cells and functional impairment of T-cell responses. The mechanistic basis of the functional impairment of the surviving cells is not clear. Indoleamine 2,3-dioxygenase (IDO) is an immunosuppressive enzyme that inhibits T-cell proliferation by catabolizing the essential amino acid tryptophan (Trp) into the kynurenine (kyn) pathway. Here, we show that IDO mRNA expression is elevated in peripheral blood mononuclear cells (PBMCs) from HIV+ patients compared with uninfected healthy controls (HCs), and that in vitro inhibition of IDO with the competitive blocker 1-methyl tryptophan (1-mT) results in increased CD4+ T-cell proliferative response in PBMCs from HIV-infected patients. We developed an in vitro model in which exposure of PBMCs from HCs to either infectious or noninfectious, R5- or X4-tropic HIV induced IDO in plasmacytoid dendritic cells (pDCs). HIV-induced IDO was not inhibited by blocking antibodies against interferon type I or type II, which, however, induced IDO in pDCs when added to PBMC cultures. Blockade of gp120/CD4 interactions with anti-CD4 Ab inhibited HIV-mediated IDO induction. Thus, induction of IDO in pDCs by HIV may contribute to the T-cell functional impairment observed in HIV/AIDS by a non–interferon-dependent mechanism.

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