Comparison of influenza and SIV specific CD8 T cell responses in macaques

• Published in: PloS one 2012-03, Vol.7 (3), p.e32431-e32431
• Main Authors: Jegaskanda, Sinthujan, Reece, Jeanette C, De Rose, Robert, Stambas, John, Sullivan, Lucy, Brooks, Andrew G, Kent, Stephen J, Sexton, Amy
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animal models; Animals; Antigenic determinants; Antigens; Apoptosis; Avidity; Biology; CD28 antigen; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - virology; Chronic Disease; Comparative analysis; Comparative studies; Cytokines; Cytotoxicity; Degranulation; Development and progression; Disease control; Effector cells; Epitope Mapping; Epitopes; Exhaustion; gamma -Interferon; Health aspects; HIV; HLA-A Antigens - chemistry; HLA-A Antigens - genetics; HLA-A Antigens - immunology; Human immunodeficiency virus; Humans; Immunity; Immunological memory; Immunology; Infections; Influenza; Influenza A Virus, H1N1 Subtype - immunology; Influenza A Virus, H3N2 Subtype - immunology; Influenza vaccines; Influenza virus; Influenza viruses; Interferon; Interleukin 2; Lymphocytes; Lymphocytes T; Macaca nemestrina; Macaca nemestrina - genetics; Macaca nemestrina - immunology; Macaca nemestrina - virology; Macrophage inflammatory protein; Major histocompatibility complex; Medicine; Memory cells; Molecular Sequence Data; Nucleoproteins - immunology; Orthomyxoviridae - immunology; Pathogens; PD-1 protein; Primates; Protein Multimerization; Protein Structure, Quaternary; Quality; Reagents; Reproducibility of Results; Simian Acquired Immunodeficiency Syndrome - immunology; Simian Acquired Immunodeficiency Syndrome - prevention & control; Simian immunodeficiency virus; Simian Immunodeficiency Virus - immunology; Species Specificity; Studies; Swine flu; T cell receptors; T cells; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - metabolism; T-Lymphocytes, Cytotoxic - virology; Tumor necrosis factor- alpha; Tumor necrosis factor-α; Vaccination; Viral infections; Viruses; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0032431

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.