CD226 expression deficiency causes high sensitivity to apoptosis in NK T cells from patients with systemic lupus erythematosus.
J Immunol
; 174(3): 1281-90, 2005 Feb 01.
Article
in En
| MEDLINE
| ID: mdl-15661884
ABSTRACT
Humans and mice with systemic lupus erythematosus (SLE) and related autoimmune diseases have reduced numbers of NK T cells. An association between NK T cell deficiency and autoimmune disease has been identified. However, the mechanisms for reduction of NK T cell number in patients with SLE are unknown. In the present study we report that NK T cells from active SLE patients are highly sensitive to anti-CD95-induced apoptosis compared with those from normal subjects and inactive SLE patients. CD226 expression is deficient on NK T cells from active SLE patients. The expression of one antiapoptotic member protein, survivin, is found to be selectively deficient in freshly isolated NK T cells from active SLE patients. CD226 preactivation significantly up-regulates survivin expression and activation, which can rescue active SLE NK T cells from anti-CD95-induced apoptosis. In transfected COS7 cells, we confirm that anti-CD95-mediated death signals are inhibited by activation of the CD226 pathway through stabilization of caspase-8 and caspase-3 and through activation of survivin. We therefore conclude that deficient expression of CD226 and survivin in NK T cells from active SLE is a molecular base of high sensitivity of the cells to anti-CD95-induced apoptosis. These observations offer a potential explanation for high apoptotic sensitivity of NK T cells from active SLE, and provide a new insight into the mechanism of reduction of NK T cell number in SLE and understanding the association between NK T cell deficiency and autoimmune diseases.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Killer Cells, Natural
/
Antigens, Differentiation, T-Lymphocyte
/
Down-Regulation
/
T-Lymphocyte Subsets
/
Apoptosis
/
Lupus Erythematosus, Systemic
Type of study:
Diagnostic_studies
/
Etiology_studies
/
Prognostic_studies
Language:
En
Journal:
J Immunol
Year:
2005
Type:
Article