Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 209, Issue 1, Pages 109-121Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20110399
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Funding
- Baylor Health Care System Foundation
- Agence Nationale de Recherches sur le SIDA (ANRS) HIV Vaccine Network
- ANRS
- Sidaction, Paris, France
- [U19 AI057234]
- MRC [MC_U117565642] Funding Source: UKRI
- Medical Research Council [MC_U117565642] Funding Source: researchfish
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Dendritic cells (DCs) can initiate and shape host immune responses toward either immunity or tolerance by their effects on antigen-specific CD4(+) T cells. DC-asialoglycoprotein receptor (DC-ASGPR), a lectinlike receptor, is a known scavenger receptor. Here, we report that targeting antigens to human DCs via DC-ASGPR, but not lectin-like oxidized-LDL receptor, Dectin-1, or DC-specific ICAM-3-grabbing nonintegrin favors the generation of antigen-specific suppressive CD4(+) T cells that produce interleukin 10 (IL-10). These findings apply to both self-and foreign antigens, as well as memory and naive CD4(+) T cells. The generation of such IL-10-producing CD4(+) T cells requires p38/extracellular signal-regulated kinase phosphorylation and IL-10 induction in DCs. We further demonstrate that immunization of nonhuman primates with antigens fused to anti-DC-ASGPR monoclonal antibody generates antigen-specific CD4(+) T cells that produce IL-10 in vivo. This study provides a new strategy for the establishment of antigen-specific IL-10-producing suppressive T cells in vivo by targeting whole protein antigens to DCs via DC-ASGPR.
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