Cytotoxic capacity of SIV-specific CD8(+) T cells against primary autologous targets correlates with immune control in SIV-infected rhesus macaques

• Published in: PLoS pathogens 2013-02, Vol.9 (2), p.e1003195
• Main Authors: Mendoza, Daniel, Migueles, Stephen A, Rood, Julia E, Peterson, Bennett, Johnson, Sarah, Doria-Rose, Nicole, Schneider, Douglas, Rakasz, Eva, Trivett, Matthew T, Trubey, Charles M, Coalter, Vicky, Hallahan, Claire W, Watkins, David, Franchini, Genoveffa, Lifson, Jeffrey D, Connors, Mark
• Format: Article
• Language: English
• Subjects: Animals; Biology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - pathology; CD8-Positive T-Lymphocytes - virology; Disease Progression; Host-Pathogen Interactions; Immunity; Macaca mulatta - immunology; Macaca mulatta - virology; Medicine; Simian Acquired Immunodeficiency Syndrome - immunology; Simian Acquired Immunodeficiency Syndrome - pathology; Simian Acquired Immunodeficiency Syndrome - virology; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - pathology; T-Lymphocytes, Cytotoxic - virology; Virus Replication
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1003195

Although the study of non-human primates has resulted in important advances for understanding HIV-specific immunity, a clear correlate of immune control over simian immunodeficiency virus (SIV) replication has not been found to date. In this study, CD8(+) T-cell cytotoxic capacity was examined to determine whether this function is a correlate of immune control in the rhesus macaque (RM) SIV infection model as has been suggested in chronic HIV infection. SIVmac251-infected human reverse transcriptase (hTERT)-transduced CD4(+) T-cell clone targets were co-incubated with autologous macaque effector cells to measure infected CD4(+) T-cell elimination (ICE). Twenty-three SIV-infected rhesus macaques with widely varying plasma viral RNA levels were evaluated in a blinded fashion. Nineteen of 23 subjects (83%) were correctly classified as long-term nonprogressor/elite controller (LTNP/EC), slow progressor, progressor or SIV-negative rhesus macaques based on measurements of ICE (weighted Kappa 0.75). LTNP/EC had higher median ICE than progressors (67.3% [22.0-91.7%] vs. 23.7% [0.0-58.0%], p = 0.002). In addition, significant correlations between ICE and viral load (r = -0.57, p = 0.01), and between granzyme B delivery and ICE (r = 0.89, p