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1.
J Immunol ; 182(12): 7587-94, 2009 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-19494282

RESUMO

We have cloned the mouse and human C-type lectin Clec12A, expressed both, and produced mAb recognizing both. Mouse Clec12A is highly expressed on splenic CD8(+) dendritic cells (DC) and plasmacytoid DC. A proportion of CD8(-)DC also expresses lower levels of Clec12A, as do monocytes, macrophages, and B cells. Human CLEC12A, like the mouse counterpart, is expressed on blood monocytes and DC, including pDC and BDCA-3(+)DC, the proposed equivalent of mouse CD8(+)DC. To determine whether Ag targeted to Clec12A could induce immune responses, mice were injected with a rat mAb recognizing Clec12A, or a control rat mAb, then production of anti-rat Ig was measured. Anti-Clec12A mAb alone produced only moderate responses, but these were amplified by coinjecting only small amounts of LPS as a DC activation agent. Furthermore, when OVA was conjugated to anti-Clec12A mAb, OVA-specific T cells were induced to proliferate. This Ag presentation to naive T cells was due to targeting conventional DC, because their ablation eliminated T cell activation. The potent Ab responses induced using microgram amounts of anti-Clec12A and minimal amounts of adjuvant demonstrate that this molecule can be used as an Ag-delivery target to enhance Ab responses to vaccines.


Assuntos
Formação de Anticorpos/imunologia , Antígenos/imunologia , Células Dendríticas/imunologia , Lectinas Tipo C/imunologia , Receptores Mitogênicos/imunologia , Animais , Apresentação de Antígeno/imunologia , Membrana Celular/imunologia , Células Cultivadas , Humanos , Leucócitos/imunologia , Camundongos
2.
J Exp Med ; 204(11): 2579-90, 2007 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-17923506

RESUMO

Interferon-producing killer dendritic cells (IKDCs) have been described as possessing the lytic potential of NK cells and the antigen-presenting capacity of dendritic cells (DCs). In this study, we examine the lytic function and antigen-presenting capacity of mouse spleen IKDCs, including those found in DC preparations. IKDCs efficiently killed NK cell targets, without requiring additional activation stimuli. However, in our hands, when exposed to protein antigen or to MHC class II peptide, IKDCs induced little or no T cell proliferation relative to conventional DCs or plasmacytoid DCs, either before or after activation with CpG, or in several disease models. Certain developmental features indicated that IKDCs resembled NK cells more than DCs. IKDCs, like NK cells, did not express the transcription factor PU.1 and were absent from recombinase activating gene-2-null, common gamma-chain-null (Rag2(-/-)Il2rg(-/-)) mice. When cultured with IL-15 and -18, IKDCs proliferated extensively, like NK cells. Under these conditions, a proportion of expanded IKDCs and NK cells expressed high levels of surface MHC class II. However, even such MHC class II(+) IKDCs and NK cells induced poor T cell proliferative responses compared with DCs. Thus, IKDCs resemble NK cells functionally, and neither cell type could be induced to be effective antigen-presenting cells.


Assuntos
Células Dendríticas/imunologia , Interferons/biossíntese , Células Matadoras Naturais/imunologia , Animais , Células Dendríticas/classificação , Antígenos de Histocompatibilidade Classe II/imunologia , Imunofenotipagem , Integrina alfa2/análise , Integrina alfa2/imunologia , Interferons/imunologia , Células Matadoras Naturais/classificação , Antígenos Comuns de Leucócito/análise , Antígenos Comuns de Leucócito/imunologia , Ativação Linfocitária , Camundongos , Baço/imunologia , Linfócitos T/imunologia
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