Abstract

Cytotoxic T lymphocytes (CTL) are likely to play an important role in limiting the spread of the human immunodeficiency virus (HIV) in infected individuals. This cellular immune response will be studied in simian immunodeficiency virus (SIV)-infected rhesus monkeys. In these studies we will assess: I. SIV CTL epitopes and restricting MHC class I molecules in rhesus monkeys. II. T cell receptor V gene usage in SIV-infected monkeys. III. The role of CTL pressure in the selection of SIV mutations. IV. Novel vaccine approaches for the generation of SIV-specific CTL. V. The contribution of CTL in the control SIV spread during primary infection.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AI020729-18
Application #
6124180
Study Section
Special Emphasis Panel (NSS)
Program Officer
Bridges, Sandra H
Project Start
1984-06-01
Project End
2002-11-30
Budget Start
1999-12-01
Budget End
2000-11-30
Support Year
18
Fiscal Year
2000
Total Cost
$515,890
Indirect Cost

  Institution

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

  Publications

Manuel, Edwin R; Yeh, Wendy W; Seaman, Michael S et al. (2009) Dominant CD8+ T-lymphocyte responses suppress expansion of vaccine-elicited subdominant T lymphocytes in rhesus monkeys challenged with pathogenic simian-human immunodeficiency virus. J Virol 83:10028-35
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
Permar, Sallie R; Rao, Srinivas S; Sun, Yue et al. (2007) Clinical measles after measles virus challenge in simian immunodeficiency virus-infected measles virus-vaccinated rhesus monkeys. J Infect Dis 196:1784-93
Hasegawa, Atsuhiko; Moriya, Chikaya; Liu, Huining et al. (2007) Analysis of TCRalphabeta combinations used by simian immunodeficiency virus-specific CD8+ T cells in rhesus monkeys: implications for CTL immunodominance. J Immunol 178:3409-17
Manuel, Edwin R; Charini, William A; Sen, Pritha et al. (2006) Contribution of T-cell receptor repertoire breadth to the dominance of epitope-specific CD8+ T-lymphocyte responses. J Virol 80:12032-40
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
Margolin, David H; Saunders, Erika H; Bronfin, Benjamin et al. (2006) Germinal center function in the spleen during simian HIV infection in rhesus monkeys. J Immunol 177:1108-19
Yeh, Wendy W; Cale, Evan M; Jaru-Ampornpan, Pimkwan et al. (2006) Compensatory substitutions restore normal core assembly in simian immunodeficiency virus isolates with Gag epitope cytotoxic T-lymphocyte escape mutations. J Virol 80:8168-77
LaBonte, Michelle L; McKay, Paul F; Letvin, Norman L (2006) Evidence of NK cell dysfunction in SIV-infected rhesus monkeys: impairment of cytokine secretion and NKG2C/C2 expression. Eur J Immunol 36:2424-33
Barouch, Dan H; Powers, Jennifer; Truitt, Diana M et al. (2005) Dynamic immune responses maintain cytotoxic T lymphocyte epitope mutations in transmitted simian immunodeficiency virus variants. Nat Immunol 6:247-52

Showing the most recent 10 out of 138 publications