Expression of NKG2D and CD107 in CD8(+) effector memory lymphocytes in Churg-Strauss syndrome.
OBJECTIVE
Churg-Strauss syndrome (CSS) is a necrotising vasculitis of small vessels in which oligoclonally expanded TCR Vβ CD8+ effector memory T cells populations (TEM) may be involved in vasculitic damage. The aim of this study was to assess the functional role of CD8+ T cells in CSS patients by flow cytometry analysis of membrane expression of cytotoxic markers NKG2D and CD107a.


METHODS
Immunostaining of peripheral T cells and effector memory lymphocytes (TEM) from CSS patients and controls was performed by gating CD28 and CD45RA in the CD8+NKG2D+ and CD4+NKG2D+ populations. CD107a expression was evaluated in both whole CD8+ and CD4+ and the TEM cells by gating CD62 and CD45RA following polyclonal stimulation.


RESULTS
NKG2D expression was shifted toward the CD8+CD28- fraction of T cells in CSS patients compared to healthy controls (56.1±25.8% versus 17.2±7.3%, respectively, p=0.002). CD8+Vβ+ expanded T cells showed a significantly increased expression of NKG2D compared to the whole CD8+ T cell population (91.4±1.9% versus 79.7±3.8%, respectively, p=0.015). Moreover the CD8+ population from CSS upregulates CD107a on its surface upon polyclonal stimulation in a significantly higher proportion than healthy subjects (26.2±10.8% versus 8.2±2.9%, p=0.0031) and the majority CD8+ CD107+ cells from CSS patients showed a TEM phenotype compared to controls (64.8±4.9% vs. 19.8±2.9, respectively, p<0.001).


CONCLUSIONS
In CSS, CD8+ TEM lymphocytes show markers of cytotoxic activity, which suggests a role for these cells in vasculitic damage.
Allergology and Clinical Immunology, University of Torino, Italy. monica.boita@libero.it
Monica
M
Boita
Giovanni
G
Rolla
Roberto
R
Mallone
Emanuela
E
Martinuzzi
Enrico
E
Heffler
Paola
P
Circosta
Angela Rita
AR
Elia
Alessandro
A
Cignetti
Sophie
S
Caillat-Zucman
Mathilde
M
de Menthon
Giuseppe
G
Guida
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D018106:CD28 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D015267:Churg-Strauss Syndrome / Q000276:immunology*; D019040:E-Selectin / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping / Q000379:methods; D007558:Italy; D017493:Leukocyte Common Antigens / Q000032:analysis; D008213:Lymphocyte Activation; D051907:Lysosomal Membrane Proteins / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000032:analysis*; D010297:Paris; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D052118:Lysosomal-Associated Membrane Protein 1
D015415:Biomarkers; D018106:CD28 Antigens; D019040:E-Selectin; D017493:Leukocyte Common Antigens; D051907:Lysosomal Membrane Proteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; D016693:Receptors, Antigen, T-Cell, alpha-beta; C527085:KLRK1 protein, human; C489116:LAMP1 protein, human; D052118:Lysosomal-Associated Membrane Protein 1; C546936:SELE protein, human