While much work has been published on the dynamics of T cells-changes in representation of CD4 and CD8 cells-during HIV disease progression and treatment (HAART), much less is known about the changes in the functional subsets of T cells. Indeed, virtually nothing is known about the changes in the mucosal T cells-those cells residing in the gut or other peripheral sites (but can traffic via the blood and are found at low frequencies there). We are investigating the interrelationship of the mucosal and central immune systems, using our unique 17-color flow cytometric technology to derive as much information as possible from each animal. We are evaluating the functional status of the dozens of unique T cell subsets in blood, lymphoid organs, and mucosal sites during SIV disease and subsequent therapeutic regimens. We are also comparing these parameters in animals that have undergone vaccine regimens, to understand whether or not the vaccines have altered the specific immune response to the virus and the impact of such changes on clinical outcome.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI005019-04
Application #
7174920
Study Section
(FCC)
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2005
Total Cost
Indirect Cost
Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Mattapallil, Joseph J; Douek, Daniel C; Buckler-White, Alicia et al. (2006) Vaccination preserves CD4 memory T cells during acute simian immunodeficiency virus challenge. J Exp Med 203:1533-41
Wille-Reece, Ulrike; Flynn, Barbara J; Lore, Karin et al. (2006) Toll-like receptor agonists influence the magnitude and quality of memory T cell responses after prime-boost immunization in nonhuman primates. J Exp Med 203:1249-58
Mattapallil, Joseph J; Hill, Brenna; Douek, Daniel C et al. (2006) Systemic vaccination prevents the total destruction of mucosal CD4 T cells during acute SIV challenge. J Med Primatol 35:217-24
Mattapallil, Joseph J; Douek, Daniel C; Hill, Brenna et al. (2005) Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infection. Nature 434:1093-7
Nishimura, Yoshiaki; Brown, Charles R; Mattapallil, Joseph J et al. (2005) Resting naive CD4+ T cells are massively infected and eliminated by X4-tropic simian-human immunodeficiency viruses in macaques. Proc Natl Acad Sci U S A 102:8000-5
Lueders, Kira K; De Rosa, Stephen C; Valentin, Antonio et al. (2004) A potent anti-HIV immunotoxin blocks spreading infection by primary HIV type 1 isolates in multiple cell types. AIDS Res Hum Retroviruses 20:145-50
Mattapallil, Joseph J; Letvin, Norman L; Roederer, Mario (2004) T-cell dynamics during acute SIV infection. AIDS 18:13-23
Brenchley, Jason M; Hill, Brenna J; Ambrozak, David R et al. (2004) T-cell subsets that harbor human immunodeficiency virus (HIV) in vivo: implications for HIV pathogenesis. J Virol 78:1160-8