Abstract

Dendritic cells (DCs) are presenting cells that stimulate strong B cell and T cell immunity in a large number of experimental systems, including CTL responses in vivo, but DCs are also known to be an important site for HIV-1 replication in patients.
Aims 1 and 2 will dissect in dendritic cells innate susceptibility mechanisms. Several genetic subtypes of HIV-1 will be tested to see if DCs exhibit greater resistance to some e.g. to clade B vs. E. The investigators recently found that certain DCs are unusually permissive to HIV-1 entry by a CD4-dependent pathway, and this will be dissected at the level of chemokine and multilectin receptors.
Aim 3 will approach neutralizing antibodies. New and existing antibodies will be tested for the capacity to bloc DC-mediated infections of human cells in vitro. High resolution SEM (with Erlandsen, U.MN) will be used to map neutralization epitopes on DCs.
These aims can pursue DCs as natural sites for HIV-1 pathogenesis and protection in vivo, and thereby improve vaccine design.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI040874-02
Application #
2653883
Study Section
Special Emphasis Panel (ZRG5-AAR (01))
Project Start
1997-02-01
Project End
2000-01-31
Budget Start
1998-02-01
Budget End
1999-01-31
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Rockefeller University
Department
Physiology
Type
Other Domestic Higher Education
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065

  Publications

Nchinda, Godwin; Amadu, David; Trumpfheller, Christine et al. (2010) Dendritic cell targeted HIV gag protein vaccine provides help to a DNA vaccine including mobilization of protective CD8+ T cells. Proc Natl Acad Sci U S A 107:4281-6
Romani, Nikolaus; Thurnher, Martin; Idoyaga, Juliana et al. (2010) Targeting of antigens to skin dendritic cells: possibilities to enhance vaccine efficacy. Immunol Cell Biol 88:424-30
Bozzacco, Leonia; Trumpfheller, Christine; Huang, Yaoxing et al. (2010) HIV gag protein is efficiently cross-presented when targeted with an antibody towards the DEC-205 receptor in Flt3 ligand-mobilized murine DC. Eur J Immunol 40:36-46
Cheong, Cheolho; Choi, Jae-Hoon; Vitale, Laura et al. (2010) Improved cellular and humoral immune responses in vivo following targeting of HIV Gag to dendritic cells within human anti-human DEC205 monoclonal antibody. Blood 116:3828-38
Cheong, Cheolho; Matos, Ines; Choi, Jae-Hoon et al. (2010) Microbial stimulation fully differentiates monocytes to DC-SIGN/CD209(+) dendritic cells for immune T cell areas. Cell 143:416-29
Flacher, Vincent; Tripp, Christoph H; Stoitzner, Patrizia et al. (2010) Epidermal Langerhans cells rapidly capture and present antigens from C-type lectin-targeting antibodies deposited in the dermis. J Invest Dermatol 130:755-62
Longhi, M Paula; Trumpfheller, Christine; Idoyaga, Juliana et al. (2009) Dendritic cells require a systemic type I interferon response to mature and induce CD4+ Th1 immunity with poly IC as adjuvant. J Exp Med 206:1589-602
Iwai, Yoshiko; Hemmi, Hiroaki; Mizenina, Olga et al. (2008) An IFN-gamma-IL-18 signaling loop accelerates memory CD8+ T cell proliferation. PLoS One 3:e2404
Trumpfheller, Christine; Caskey, Marina; Nchinda, Godwin et al. (2008) The microbial mimic poly IC induces durable and protective CD4+ T cell immunity together with a dendritic cell targeted vaccine. Proc Natl Acad Sci U S A 105:2574-9
Idoyaga, Juliana; Cheong, Cheolho; Suda, Koji et al. (2008) Cutting edge: langerin/CD207 receptor on dendritic cells mediates efficient antigen presentation on MHC I and II products in vivo. J Immunol 180:3647-50

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