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Lytic Granule Loading of CD8(+) T Cells Is Required for HIV-Infected Cell Elimination Associated with Immune Control

  1. Author:
    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.

  2. Author Address

    Migueles, Stephen A.; Osborne, Christine M.; Royce, Cassandra, Compton, Alex A.; Joshi, Rohan P.; Weeks, Kristin A.; Rood, Julia E.; Berkley, Amy M.; Cogliano-Shutta, Nancy A.; Lloyd, Margaret, Roby, Gregg, Kwan, Richard, McLaughlin, Mary, Stallings, Sara, Rehm, Catherine, O'Shea, Marie A.; Mican, JoAnn, Hallahan, Claire W.; Follman, Dean A.; Connors, Mark] NIAID, NIH, Bethesda, MD 20892 USA. [Sacha, Jonah B.] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53719 USA. [Packard, Beverly Z.; Komoriya, Akira] Oncolmmunin, Gaithersburg, MD 20877 USA. [Palmer, Sarah, Wiegand, Ann P.; Maldarelli, Frank, Coffin, John M.] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. [Mellors, John W.] Univ Pittsburgh, Med Ctr, Div Infect Dis, Pittsburgh, PA 15261 USA.
    1. Year: 2008
  2. Journal: Immunity
    1. 29
    2. 6
    3. Pages: 1009-1021
  4. Type of Article: Article
  1. Abstract:

    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 CDB+ 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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External Sources

  1. PMID: 19062316

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