Distribution, persistence, and efficacy of adoptively transferred central and effector memory-derived autologous simian immunodeficiency virus-specific CD8+ T cell clones in rhesus macaques during acute infection.
Plasma viremia decreases coincident with the appearance of virus-specific CD8(+) T cells during acute HIV or SIV infection. This finding, along with demonstrations of viral mutational escape from CD8(+) T cell responses and transient increase in plasma viremia after depletion of CD8(+) T cells in SIV-infected monkeys strongly suggest a role for CD8(+) T cells in controlling HIV/SIV. However, direct quantitative or qualitative correlates between CD8(+) T cell activity and virus control have not been established. To directly assess the impact of large numbers of virus-specific CD8(+) T cells present at time of SIV infection, we transferred in vitro expanded autologous central and effector memory-derived Gag CM9-, Nef YY9-, and Vif WY8-specific CD8(+) T cell clones to acutely infected rhesus macaques. The cells persisted in PBMCs between 4 and 9 d, but were not detected in gut-associated lymphoid tissue or lymph nodes. Interestingly, a high frequency of the infused cells localized to the lungs, where they persisted at high frequency for >6 wk. Although persisting cells in the lungs were Ag reactive, there was no measurable effect on virus load. Sequencing of virus from the animal receiving Nef YY9-specific CD8(+) T cells demonstrated an escape mutation in this epitope <3 wk postinfection, consistent with immune selection pressure by the infused cells. These studies establish methods for adoptive transfer of autologous SIV-specific CD8(+) T cells for evaluating immune control during acute infection and demonstrate that infused cells retain function and persist for at least 2 mo in specific tissues.
Minang
Jacob T
JT
AIDS and Cancer Virus Program, SAIC-Frederick, Frederick, MD 21702, USA.
Trivett
Matthew T
MT
Bolton
Diane L
DL
Trubey
Charles M
CM
Estes
Jacob D
JD
Li
Yuan
Y
Smedley
Jeremy
J
Pung
Rhonda
R
Rosati
Margherita
M
Jalah
Rashmi
R
Pavlakis
George N
GN
Felber
Barbara K
BK
Piatak
Michael
M
Roederer
Mario
M
Lifson
Jeffrey D
JD
Ott
David E
DE
Ohlen
Claes
C
D019264:Adoptive Transfer; D000818:Animals; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D002999:Clone Cells; D004279:DNA, Viral / Q000235:genetics; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D005434:Flow Cytometry; D057131:Immune Evasion / Q000235:genetics; D007156:Immunologic Memory; D008213:Lymphocyte Activation / Q000276:immunology; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D014766:Viremia / Q000276:immunology
D004279:DNA, Viral; D018984:Epitopes, T-Lymphocyte