Trafficking, persistence, and activation state of adoptively transferred allogeneic and autologous Simian Immunodeficiency Virus-specific CD8(+) T cell clones during acute and chronic infection of rhesus macaques.
Despite multiple lines of evidence suggesting their involvement, the precise role of CD8(+) T cells in controlling HIV replication remains unclear. To determine whether CD8(+) T cells can limit retroviral replication in the absence of other immune responses, we transferred 1-13 x 10(9) allogeneic in vitro expanded SIV-specific CD8(+) T cell clones matched for the relevant restricting MHC-I allele into rhesus macaques near the time of i.v. SIV challenge. Additionally, in vitro expanded autologous SIV-specific CD8(+) T cell clones were infused 4-9 mo postinfection. Infused cells did not appreciably impact acute or chronic viral replication. The partially MHC-matched allogeneic cells were not detected in the blood or most tissues after 3 d but persisted longer in the lungs as assessed by bronchoalveolar lavage (BAL). Autologous cells transferred i.v. or i.p. were found in BAL and blood samples for up to 8 wk postinfusion. Interestingly, despite having a nominally activated phenotype (CD69(+)HLA-DR(+)), many of these cells persisted in the BAL without dividing. This suggests that expression of such markers by T cells at mucosal sites may not reflect recent activation, but may instead identify stable resident memory T cells. The lack of impact following transfer of such a large number of functional Ag-specific CD8(+) T cells on SIV replication may reflect the magnitude of the immune response required to contain the virus.
Bolton
Diane L
DL
ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Minang
Jacob T
JT
Trivett
Matthew T
MT
Song
Kaimei
K
Tuscher
Jennifer J
JJ
Li
Yuan
Y
Piatak
Michael
M
O'Connor
David
D
Lifson
Jeffrey D
JD
Roederer
Mario
M
Ohlen
Claes
C
D019264:Adoptive Transfer; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D002908:Chronic Disease; D002999:Clone Cells; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology
D000945:Antigens, Differentiation, T-Lymphocyte; D015395:Histocompatibility Antigens Class I