title: CD226 expression deficiency causes high sensitivity to apoptosis in NK T cells from patients with systemic lupus erythematosus.
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.
authors.affiliation: Department of Internal Medicine, Renmin Hospital, Wuhan University, Wuhan, Peoples Republic of China.
authors.forename: Deng
authors.initials: D
authors.lastname: Tao
authors.forename: Liu
authors.initials: L
authors.lastname: Shangwu
authors.forename: Wu
authors.initials: W
authors.lastname: Qun
authors.forename: Liu
authors.initials: L
authors.lastname: Yan
authors.forename: Ju
authors.initials: J
authors.lastname: Wei
authors.forename: Liu
authors.initials: L
authors.lastname: Junyan
authors.forename: Gong
authors.initials: G
authors.lastname: Feili
authors.forename: Jin
authors.initials: J
authors.lastname: Boquan
authors.forename: Tan
authors.initials: T
authors.lastname: Jinquan
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D019556:COS Cells; D002522:Chlorocebus aethiops; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D005260:Female; D020868:Gene Silencing / Q000276:immunology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D008875:Middle Aged; D009363:Neoplasm Proteins; D011241:Prednisone / Q000627:therapeutic use; D000077022:Survivin; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014162:Transfection; D019014:fas Receptor / Q000235:genetics / Q000276:immunology; D000098862:T Lineage-Specific Activation Antigen 1
chemical_list: D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; C107489:BIRC5 protein, human; D000098862:T Lineage-Specific Activation Antigen 1; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; D019014:fas Receptor; D011241:Prednisone