Abstract

Significant new advances were made in discovering mechanisms by which regulatory T cells suppressed anti-viral CD8+ T cell responses in mice chronically infected with Friend retrovirus. A new in vitro assay for detecting Treg-mediated suppression of CD8+ T cell function was developed in which virtually all aspects of in vivo responses are replicated. This system will enable us to directly study intereactions between purified subsets of T cells. Our new information is leading to new avenues for modulating interactions between these critical components of antiviral immunity leading to treatments for chronic retroviral infections. Recent reports indicate that regulatory T cell suppression of CD8+ T cell resopnses is also occurring in HIV infections in humans and the degree of suppression correlates with viral loads. Thus our mouse model is extremely relvant to human retroviral infections and may lead to new therapies to treat chronic HIV infections.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000753-11
Application #
7302662
Study Section
(LPVD)
Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
2006
Total Cost
Indirect Cost

  Institution

Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Velmourougane, Geetha; Harbut, Michael B; Dalal, Seema et al. (2011) Synthesis of new (-)-bestatin-based inhibitor libraries reveals a novel binding mode in the S1 pocket of the essential malaria M1 metalloaminopeptidase. J Med Chem 54:1655-66
Ammann, Christoph G; Messer, Ronald J; Peterson, Karin E et al. (2009) Lactate dehydrogenase-elevating virus induces systemic lymphocyte activation via TLR7-dependent IFNalpha responses by plasmacytoid dendritic cells. PLoS One 4:e6105
Pike, Rebecca; Filby, Andrew; Ploquin, Mickael J-Y et al. (2009) Race between retroviral spread and CD4+ T-cell response determines the outcome of acute friend virus infection. J Virol 83:11211-22
Robertson, Shelly J; Messer, Ronald J; Carmody, Aaron B et al. (2008) CD137 costimulation of CD8+ T cells confers resistance to suppression by virus-induced regulatory T cells. J Immunol 180:5267-74
Greene, Justin M; Burwitz, Benjamin J; Blasky, Alex J et al. (2008) Allogeneic lymphocytes persist and traffic in feral MHC-matched mauritian cynomolgus macaques. PLoS One 3:e2384
Santiago, Mario L; Montano, Mauricio; Benitez, Robert et al. (2008) Apobec3 encodes Rfv3, a gene influencing neutralizing antibody control of retrovirus infection. Science 321:1343-6
Marques, Rute; Antunes, Ines; Eksmond, Urszula et al. (2008) B lymphocyte activation by coinfection prevents immune control of friend virus infection. J Immunol 181:3432-40
Robertson, Shelly J; Ammann, Christoph G; Messer, Ronald J et al. (2008) Suppression of acute anti-friend virus CD8+ T-cell responses by coinfection with lactate dehydrogenase-elevating virus. J Virol 82:408-18
Hasenkrug, Kim J; Dittmer, Ulf (2007) Immune control and prevention of chronic Friend retrovirus infection. Front Biosci 12:1544-51
Hasenkrug, Kim J (2007) The leptin connection: regulatory T cells and autoimmunity. Immunity 26:143-5

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