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Peptide-based Identification of Functional Motifs and their Binding Partners
Published on: July 1, 2013
Expression of zeta molecules is decreased in NK cells from HIV-infected patients
M F Geertsma1, A Stevenhagen, E M van Dam
1Department Infectious Diseases, Leiden University Medical Center, P. O. Box 9600, 2300 RC, Leiden, The Netherlands. geertsma@stad.dsl.nl
Insights
Natural killer (NK) cell activity declines in HIV infection due to reduced zeta-chain expression. This impairment in zeta-chain signaling molecules correlates with disease progression and defective NK cell cytolysis.
Area of Science:
- Immunology
- Virology
- Cellular Biology
Background:
- Natural killer (NK) cell cytolysis is crucial for immune surveillance.
- HIV infection is known to impair NK cell function.
- Zeta (ζ) chain molecules are critical for signal transduction in NK cells upon receptor ligation.
Purpose of the Study:
- To investigate if zeta (ζ) chain expression is reduced in NK cells during HIV infection.
- To determine if reduced zeta (ζ) chain expression correlates with impaired NK cell cytolytic activity.
- To explore the relationship between zeta (ζ) chain expression, CD16 expression, and NK cell function in HIV-infected individuals.
Main Methods:
- Flow cytometry (FACS) was used to analyze zeta (ζ) chain and CD16 expression on NK cells.
- Assessment of CD16-dependent and CD16-independent NK cell-mediated cytolysis.
- Correlation analysis between zeta (ζ) chain expression, CD16 expression, and cytolytic function.
Main Results:
- NK cells from patients with Acquired Immunodeficiency Syndrome (AIDS) showed significantly lower zeta (ζ) chain expression compared to non-AIDS patients and healthy controls.
- CD16-dependent NK cell cytolysis positively correlated with both zeta (ζ) chain and CD16 expression.
- No correlation was found between CD16-independent cytolysis and zeta (ζ) chain expression.
Conclusions:
- Reduced zeta (ζ) chain expression in NK cells from HIV-infected individuals correlates with disease progression.
- The diminished expression of zeta (ζ) molecules may partially explain the defective NK cell-mediated cytolysis observed in HIV infection.
Abstract:
Cytolysis by natural killer (NK) cells is impaired in HIV infection. We investigated whether the expression of zeta (zeta) molecules, essential elements of signalling initiated upon ligation of, e.g., CD16, is reduced and if so, whether this reduction could be involved in defective cytolysis. FACS analysis revealed significantly lower levels of zeta in NK cells from AIDS patients compared to cells from patients without AIDS and healthy controls. CD16-dependent cytolysis by NK cells correlated with expression of zeta molecules and CD16, the latter possibly related to zeta expression. No correlation was observed between CD16-independent cytolysis and zeta expression. Reduced expression of zeta molecules by NK cells from HIV-infected patients thus correlates with disease progression and may, in part, explain the defective cytolysis by these cells.
