Onderzoek van Marshall-Gradisnik en collega's naar de celadhesiemoleculen op en de (cytotoxische)

"wapens" (granzyme A en B, perforine) van vier typen Natural Killer (NK)-cellen (CD56brightCD16-/dim,

CD56dimCD16-, CD56dimCD16+ or CD56-CD16+ NK cellen) laten een aantal afwijkingen zien:

verrminderde expressie van celadhesiemoleculen CD2 en CD18 op CD56brightCD16-/dim cellen,

verhoogde expressie van de celadhesiemolecuul CD57 op CD56dimCD16+ NK cellen, en

verminderde hoeveelheden granzyme B in CD56dimCD16+ and CD56-CD16+ NK cellen.

CD2 en CD18 worden door de onderzoekers gerelateerd aan afgenomen "verplaatsingssnelheid",

CD57 aan verhoogde celdeling als gevolg van blootstelling aan pathogenen en/of cytokines, en

granzyme B aan de verminderde werking "cytotoxiciteit" van de twee typen NK-cellen.

Characterization of Natural Killer cell phenotypes

in chronic fatigue syndrome/myalgic encephalomyelitis.

J Clin Cell Immunol. 2014. 5: 223. doi:10.4172/2155-9899.1000223

Huth TK, Brenu EW, Nguyen T, Hardcastle SL, Johnston S, Ramos S, Staines DR, Marshall-Gradisnik SM.

Received date: April 22, 2014,

Accepted date: June 7, 2014,

Published date: June 14, 2014

Abstract

Objective:

Natural Killer (NK) cells are classified into different phenotypes

according to the expression of the surface markers CD56 and CD16.

Each NK cell phenotype has a role in the immune response

through cytotoxic activity or cytokine production.

Reduced NK cell cytotoxic activity is a consistent finding

in patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) and

investigations into the potential causes of reduced NKcell cytotoxic activity

have predominantly focused on total NK cells.

The purpose of this study was

to investigate and characterize four NK cell phenotypes in CFS/ME.

Methods:

Twenty nine CFS/ME patients (mean age ± SEM=48.28 ± 2.63)

meeting the 1994 Fukuda definition

and 27 healthy controls (mean age ± SEM=49.15 ± 2.51)

were included in this study.

Flow cytometric protocols identified

CD56brightCD16-/dim, CD56dimCD16-, CD56dimCD16+ or CD56-CD16+ NK cells

for the measurement of surface markers

including adhesion moleculesCD2, CD18, CD11a, CD11b and CD11c,

natural cytotoxicity receptors, Killer Immunoglobulin Like Receptors,

signalling lymphocytic activation molecules and cell maturation (CD57).

Following stimulation,

NK cell phenotype expression of CD107a and CD107b

was measured as a marker for degranulation.

Intracellular staining measured lytic proteins

including perforin, Granzyme A and Granzyme B

in the four NK cell phenotypes.

Results:

In the CFS/ME group, CD56brightCD16-/dim NK cell co-expression of

adhesion molecules CD2 and CD18 was significantly reduced.

Granzyme B was significantly decreased

in CD56dimCD16+ and CD56-CD16+ NK cells

from CFS/ME patients.

CD57 expression on CD56dimCD16+ NK cells

from CFS/ME patients was significantly increased.

Conclusion:

This is the first study to characterize

four NK cell phenotypes in CFS/ME

by investigating surface and intracellular molecules

necessary for NK cell effector function.

The data suggests that

a combination of impairments in CD56dimCD16+ NK cells from CFS/ME patients

may contribute to reduced cytotoxic activity of this phenotype.

Keywords:

Natural Killer cell; Phenotypes; Chronic Fatigue Syndrome; Cytotoxic activity;

Adhesion molecules; Degranulation; Granzyme B; Cell maturation

http://omicsonline.org/open-access/

characterization-of-natural-killer-cell-phenotypes-in-chronic-fatigue-syndrome-2155-9899.1000223.pdf