Cytotoxic capacity of SIV-specific CD8(+) T cells against primary autologous targets correlates with immune control in SIV-infected rhesus macaques.
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 de...
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Public Library of Science (PLoS)
2013-02-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1003195&type=printable |
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| author | Daniel Mendoza Stephen A Migueles Julia E Rood Bennett Peterson Sarah Johnson Nicole Doria-Rose Douglas Schneider Eva Rakasz Matthew T Trivett Charles M Trubey Vicky Coalter Claire W Hallahan David Watkins Genoveffa Franchini Jeffrey D Lifson Mark Connors |
| author_facet | Daniel Mendoza Stephen A Migueles Julia E Rood Bennett Peterson Sarah Johnson Nicole Doria-Rose Douglas Schneider Eva Rakasz Matthew T Trivett Charles M Trubey Vicky Coalter Claire W Hallahan David Watkins Genoveffa Franchini Jeffrey D Lifson Mark Connors |
| author_sort | Daniel Mendoza |
| collection | DOAJ |
| description | 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<0.001) were observed. Furthermore, the CD8(+) T cells of LTNP/EC exhibited higher per-cell cytotoxic capacity than those of progressors (p = 0.004). These findings support that greater lytic granule loading of virus-specific CD8(+) T cells and efficient delivery of active granzyme B to SIV-infected targets are associated with superior control of SIV infection in rhesus macaques, consistent with observations of HIV infection in humans. Therefore, such measurements appear to represent a correlate of control of viral replication in chronic SIV infection and their role as predictors of immunologic control in the vaccine setting should be evaluated. |
| format | Article |
| id | doaj-art-e6ac21eaaf154a5ab923f12404de0e7c |
| institution | OA Journals |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2013-02-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS Pathogens |
| spelling | doaj-art-e6ac21eaaf154a5ab923f12404de0e7c2025-08-20T02:30:37ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742013-02-0192e100319510.1371/journal.ppat.1003195Cytotoxic capacity of SIV-specific CD8(+) T cells against primary autologous targets correlates with immune control in SIV-infected rhesus macaques.Daniel MendozaStephen A MiguelesJulia E RoodBennett PetersonSarah JohnsonNicole Doria-RoseDouglas SchneiderEva RakaszMatthew T TrivettCharles M TrubeyVicky CoalterClaire W HallahanDavid WatkinsGenoveffa FranchiniJeffrey D LifsonMark ConnorsAlthough 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<0.001) were observed. Furthermore, the CD8(+) T cells of LTNP/EC exhibited higher per-cell cytotoxic capacity than those of progressors (p = 0.004). These findings support that greater lytic granule loading of virus-specific CD8(+) T cells and efficient delivery of active granzyme B to SIV-infected targets are associated with superior control of SIV infection in rhesus macaques, consistent with observations of HIV infection in humans. Therefore, such measurements appear to represent a correlate of control of viral replication in chronic SIV infection and their role as predictors of immunologic control in the vaccine setting should be evaluated.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1003195&type=printable |
| spellingShingle | Daniel Mendoza Stephen A Migueles Julia E Rood Bennett Peterson Sarah Johnson Nicole Doria-Rose Douglas Schneider Eva Rakasz Matthew T Trivett Charles M Trubey Vicky Coalter Claire W Hallahan David Watkins Genoveffa Franchini Jeffrey D Lifson Mark Connors Cytotoxic capacity of SIV-specific CD8(+) T cells against primary autologous targets correlates with immune control in SIV-infected rhesus macaques. PLoS Pathogens |
| title | Cytotoxic capacity of SIV-specific CD8(+) T cells against primary autologous targets correlates with immune control in SIV-infected rhesus macaques. |
| title_full | Cytotoxic capacity of SIV-specific CD8(+) T cells against primary autologous targets correlates with immune control in SIV-infected rhesus macaques. |
| title_fullStr | Cytotoxic capacity of SIV-specific CD8(+) T cells against primary autologous targets correlates with immune control in SIV-infected rhesus macaques. |
| title_full_unstemmed | Cytotoxic capacity of SIV-specific CD8(+) T cells against primary autologous targets correlates with immune control in SIV-infected rhesus macaques. |
| title_short | Cytotoxic capacity of SIV-specific CD8(+) T cells against primary autologous targets correlates with immune control in SIV-infected rhesus macaques. |
| title_sort | cytotoxic capacity of siv specific cd8 t cells against primary autologous targets correlates with immune control in siv infected rhesus macaques |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1003195&type=printable |
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