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

By S. Migueles, C. M. Osborne, C. Royce, Alex A. Compton, Rohan Joshi, K. A. Weeks, Julia E. Rood, Amy M Berkley, J. Sacha, N. A. Cogliano-Shutta and 18 more. Immunity, 2008

602 citations recorded by the source corpus.

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.

Subfields: Immunology, Virology

View Paper: https://www.semanticscholar.org/paper/93a99341d47019e5f614499f0391e03527c55a63

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

  1. L. Shan
  2. J. Margolick
  3. R. Siliciano
  4. K. Deng
  5. Hao Zhang
  6. Hung‐Chih Yang
  7. S. A. Rabi
  8. C. Durand

Citations in the corpus