Subdominant CD8+ T-cell responses are involved in durable control of AIDS virus replication.
"Elite controllers" are individuals that durably control human immunodeficiency virus or simian immunodeficiency virus replication without therapeutic intervention. The study of these rare individuals may facilitate the definition of a successful immune response to immunodeficiency viruses. Here we describe six Indian-origin rhesus macaques that have controlled replication of the pathogenic virus SIVmac239 for 1 to 5 years. To determine which lymphocyte populations were responsible for this control, we transiently depleted the animals' CD8+ cells in vivo. This treatment resulted in 100- to 10,000-fold increases in viremia. When the CD8+ cells returned, control was reestablished and the levels of small subsets of previously subdominant CD8+ T cells expanded up to 2,500-fold above pre-depletion levels. This wave of CD8+ T cells was accompanied by robust Gag-specific CD4 responses. In contrast, CD8+ NK cell frequencies changed no more than threefold. Together, our data suggest that CD8+ T cells targeting a small number of epitopes, along with broad CD4+ T-cell responses, can successfully control the replication of the AIDS virus. It is likely that subdominant CD8+ T-cell populations play a key role in maintaining this control.
Friedrich
Thomas C
TC
Wisconsin National Primate Research Center, 1220 Capitol Court, Madison, WI 53715-1299, USA. thomasf@primate.wisc.edu
Valentine
Laura E
LE
Yant
Levi J
LJ
Rakasz
Eva G
EG
Piaskowski
Shari M
SM
Furlott
Jessica R
JR
Weisgrau
Kimberly L
KL
Burwitz
Benjamin
B
May
Gemma E
GE
León
Enrique J
EJ
Soma
Taeko
T
Napoe
Gnankang
G
Capuano
Saverio V
SV
Wilson
Nancy A
NA
Watkins
David I
DI
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology*; D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015683:Gene Products, gag / Q000276:immunology; D014644:Genetic Variation / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology; D018655:Lymphocyte Count; D008253:Macaca mulatta; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D014779:Virus Replication
D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag