title: Comparison of influenza and SIV specific CD8 T cell responses in macaques.
abstract: Macaques are a potentially useful non-human primate model to compare memory T-cell immunity to acute virus pathogens such as influenza virus and effector T-cell responses to chronic viral pathogens such as SIV. However, immunological reagents to study influenza CD8(+) T-cell responses in the macaque model are limited. We recently developed an influenza-SIV vaccination model of pigtail macaques (Macaca nemestrina) and used this to study both influenza-specific and SIV-specific CD8(+) T-cells in 39 pigtail macaques expressing the common Mane-A*10(+) (Mane-A01*084) MHC-I allele. To perform comparative studies between influenza and SIV responses a common influenza nucleoprotein-specific CD8(+) T-cell response was mapped to a minimal epitope (termed RA9), MHC-restricted to Mane-A*10 and an MHC tetramer developed to study this response. Influenza-specific memory CD8(+) T-cell response maintained a highly functional profile in terms of multitude of effector molecule expression (CD107a, IFN-γ, TNF-α, MIP-1β and IL-2) and showed high avidity even in the setting of SIV infection. In contrast, within weeks following active SIV infection, SIV-specific CD8(+) effector T-cells expressed fewer cytokines/degranulation markers and had a lower avidity compared to influenza specific CD8(+) T-cells. Further, the influenza specific memory CD8 T-cell response retained stable expression of the exhaustion marker programmed death-marker-1 (PD-1) and co-stimulatory molecule CD28 following infection with SIV. This contrasted with the effector SIV-specific CD8(+) T-cells following SIV infection which expressed significantly higher amounts of PD-1 and lower amounts of CD28. Our results suggest that strategies to maintain a more functional CD8(+) T-cell response, profile may assist in controlling HIV disease.
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Sinthujan
authors.initials: S
authors.lastname: Jegaskanda
authors.forename: Jeanette C
authors.initials: JC
authors.lastname: Reece
authors.forename: Robert
authors.initials: R
authors.lastname: De Rose
authors.forename: John
authors.initials: J
authors.lastname: Stambas
authors.forename: Lucy
authors.initials: L
authors.lastname: Sullivan
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Brooks
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kent
authors.forename: Amy
authors.initials: A
authors.lastname: Sexton
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D002908:Chronic Disease; D018604:Epitope Mapping; D015234:HLA-A Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D008254:Macaca nemestrina / Q000235:genetics / Q000276:immunology* / Q000821:virology*; D008969:Molecular Sequence Data; D009698:Nucleoproteins / Q000276:immunology; D009975:Orthomyxoviridae / Q000276:immunology*; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D015203:Reproducibility of Results; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013045:Species Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism / Q000821:virology; D014611:Vaccination
chemical_list: D015234:HLA-A Antigens; D009698:Nucleoproteins