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Lytic Granule Loading of CD8+ T Cells Is Required for HIV-Infected Cell Elimination Associated with Immune Control
Open accessAbstract
SUMMARY Virus-specific CD8+ T cells probably mediate control over HIV replication in rare individuals, termed long-term nonprogressors (LTNPs) or elite controllers. Despite extensive investigation, the mechanisms responsible for this control remain incompletely understood. We observed that HIV-specific CD8+ T cells of LTNPs persisted at higher frequencies than those of treated progressors with equally low amounts of HIV. Measured on a per-cell basis, HIV-specific CD8+ T cells of LTNPs efficiently eliminated primary autologous HIV-infected CD4+ T cells. This function required lytic granule loading of effectors and delivery of granzyme B to target cells. Defective cytotoxicity of progressor effectors could be restored after treatment with phorbol ester and calcium ionophore. These results establish an effector function and mechanism that clearly segregate with immunologic control of HIV. They also demonstrate that lytic granule contents of memory cells are a critical determinant of cytotoxicity that must be induced for maximal per-cell killing capacity.
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Cites
PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression
Day, C. L., Kaufmann, D. E., Kiepiela, P., Brown, J. A., Moodley, E. S., Reddy, S., Mackey, E. W., Miller, J. D., Leslie, A. J., DePierres, C., et al. (2006) · Nature · doi:10.1038/nature05115 · Cited by 2,680
Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction
Trautmann, L., Janbazian, L., Chomont, N., Said, E. A., Gimmig, S., Bessette, B., Boulassel, M.-R., Delwart, E., Sepulveda, H., Balderas, R. S., et al. (2006) · Nature Medicine · doi:10.1038/nm1482 · Cited by 1,565
PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection
Petrovas, C., Casazza, J. P., Brenchley, J. M., Price, D. A., Gostick, E., Adams, W. C., Precopio, M. L., Schacker, T., Roederer, M., Douek, D. C., et al. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20061496 · Cited by 889
Cited by
Wherry, E. J. (2011) · Nature Immunology · doi:10.1038/ni.2035 · Cited by 4,062
Shin, H., Blackburn, S. D., Intlekofer, A. M., Kao, C., Angelosanto, J. M., Reiner, S. L., & Wherry, E. J. (2009) · Immunity · doi:10.1016/j.immuni.2009.06.019 · Cited by 481
MAIT cells are licensed through granzyme exchange to kill bacterially sensitized targets
Kurioka, A., Ussher, J. E., Cosgrove, C., Clough, C., Fergusson, J. R., Smith, K., Kang, Y.-H., Walker, L. J., Hansen, T. H., Willberg, C. B., et al. (2015) · Mucosal Immunology · doi:10.1038/mi.2014.81 · Cited by 398
CD8+ T cells in HIV control, cure and prevention
Collins, D. R., Gaiha, G. D., & Walker, B. D. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-020-0274-9 · Cited by 303
Buggert, M., Tauriainen, J., Yamamoto, T., Frederiksen, J., Ivarsson, M. A., Michaëlsson, J., Lund, O., Hejdeman, B., Jansson, M., Sönnerborg, A., et al. (2014) · PLoS Pathogens · doi:10.1371/journal.ppat.1004251 · Cited by 296
Metadata
- Authors
- Migueles, S. A., Osborne, C. M., Royce, C., Compton, A. A., Joshi, R. P., Weeks, K. A., Rood, J. E., Berkley, A. M., Sacha, J. B., Cogliano-Shutta, N. A., Lloyd, M., Roby, G., Kwan, R., McLaughlin, M., Stallings, S., Rehm, C., O'Shea, M. A., Mican, J., Packard, B. Z., Komoriya, A., Palmer, S., Wiegand, A. P., Maldarelli, F., Coffin, J. M., Mellors, J. W., Hallahan, C. W., Follman, D. A., & Connors, M.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2008-12
- Volume
- 29
- Issue
- 6
- Pages
- 1009-1021
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2039473791
- Cited by
- 590
- References
- 3
- FWCI
- 16.67
- Type
- journal article
- Language
- en
- Open access
- bronze
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- The paper
- Migueles, S. A., Osborne, C. M., Royce, C., Compton, A. A., Joshi, R. P., Weeks, K. A., Rood, J. E., Berkley, A. M., Sacha, J. B., Cogliano-Shutta, N. A., Lloyd, M., Roby, G., Kwan, R., McLaughlin, M., Stallings, S., Rehm, C., O'Shea, M. A., Mican, J., Packard, B. Z., . . . Connors, M. (2008). Lytic Granule Loading of CD8+ T Cells Is Required for HIV-Infected Cell Elimination Associated with Immune Control. Immunity. https://doi.org/10.1016/j.immuni.2008.10.010
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
