Abstract

(from abstract): The control of virus replication in primary HIV-1 infection and disease following infection are correlated with the magnitude of the CD8+ T lymphocyte response. The central role of this CD8+ lymphocyte mediated cellular immune response in controlling virus replication has recently been demonstrated directly using the simian immunodeficiency virus of macaques (SIVmac)/rhesus monkey model of AIDS. However, a more detailed characterization of the anatomic distribution and functions mediated by CD8+ lymphocytes is essential for developing strategies to prevent or treat HIV-1 infection. In particular, the mechanism by which virus replication is controlled, the anatomic distribution of these virus-specific CD8+ lymphocytes among various lymphoid tissues and the potential contribution of these cells to AIDS pathogenesis are not fully understood. This is an amended application proposing to explore the anatomic distribution of SIV-specific CTL and the role of CD8+lymphocytes in the immunopathogenesis of CD4+T cell decline in AIDS virus infection. Specifically, 1. Describe the anatomic distribution of SIVmac-specific CD8+ T lymphocytes in primary infection and 2. Determine the contribution of CD8+ lymphocytes to the loss of CD4+ Tcells following infection by SIVmac or the rapidly CD4+T cell-depleting virus SHIV-KB9.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI048394-02
Application #
6488769
Study Section
AIDS and Related Research 8 (AARR)
Program Officer
Plaeger, Susan F
Project Start
2001-01-01
Project End
2004-12-31
Budget Start
2002-01-01
Budget End
2002-12-31
Support Year
2
Fiscal Year
2002
Total Cost
$432,000
Indirect Cost

  Institution

Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02215

  Publications

Kim, Eun-Young; Veazey, Ronald S; Zahn, Roland et al. (2008) Contribution of CD8+ T cells to containment of viral replication and emergence of mutations in Mamu-A*01-restricted epitopes in Simian immunodeficiency virus-infected rhesus monkeys. J Virol 82:5631-5
Veazey, Ronald S; Acierno, Paula M; McEvers, Kimberly J et al. (2008) Increased loss of CCR5+ CD45RA- CD4+ T cells in CD8+ lymphocyte-depleted Simian immunodeficiency virus-infected rhesus monkeys. J Virol 82:5618-30
Newberg, Michael H; McEvers, Kimberly J; Gorgone, Darci A et al. (2006) Immunodomination in the evolution of dominant epitope-specific CD8+ T lymphocyte responses in simian immunodeficiency virus-infected rhesus monkeys. J Immunol 176:319-28
Schmitz, Jorn E; Johnson, R Paul; McClure, Harold M et al. (2005) Effect of CD8+ lymphocyte depletion on virus containment after simian immunodeficiency virus SIVmac251 challenge of live attenuated SIVmac239delta3-vaccinated rhesus macaques. J Virol 79:8131-41
Sun, Yue; Schmitz, Jorn E; Acierno, Paula M et al. (2005) Dysfunction of simian immunodeficiency virus/simian human immunodeficiency virus-induced IL-2 expression by central memory CD4+ T lymphocytes. J Immunol 174:4753-60
Subbramanian, Ramu A; Moriya, Chikaya; Martin, Kristi L et al. (2004) Engineered T-cell receptor tetramers bind MHC-peptide complexes with high affinity. Nat Biotechnol 22:1429-34
Baig, Jamal; Levy, Daniel B; McKay, Paul F et al. (2002) Elicitation of simian immunodeficiency virus-specific cytotoxic T lymphocytes in mucosal compartments of rhesus monkeys by systemic vaccination. J Virol 76:11484-90
Schmitz, J E; Veazey, R S; Kuroda, M J et al. (2001) Simian immunodeficiency virus (SIV)-specific cytotoxic T lymphocytes in gastrointestinal tissues of chronically SIV-infected rhesus monkeys. Blood 98:3757-61