000			04976nam a22005777a 4500
008			180818s20182018 xxu||||| |||| 00| 0 eng d
022			_a1088-5412
024			_a10.2500/aap.2018.39.4113 [doi]
040			_aOvid MEDLINE(R)
099			_a29490770
245			_aIn vitro induction of T regulatory cells by a methylated CpG DNA sequence in humans: Potential therapeutic applications in allergic and autoimmune diseases.
251			_aAllergy & Asthma Proceedings. 39(2):143-152, 2018 Mar 01.
252			_aAllergy Asthma Proc. 39(2):143-152, 2018 Mar 01.
253			_aAllergy and asthma proceedings
260			_c2018
260			_fFY2018
266			_d2018-08-16
520			_aBACKGROUND: Allergic and autoimmune diseases comprise a group of inflammatory disorders caused by aberrant immune responses in which CD25+ Forkhead box P3-positive (FOXP3+) T regulatory (Treg) cells that normally suppress inflammatory events are often poorly functioning. This has stimulated an intensive investigative effort to find ways of increasing Tregs as a method of therapy for these conditions. One such line of investigation includes the study of how ligation of Toll-like receptors (TLRs) by CpG oligonucleotides (ODN) results in an immunostimulatory cascade that leads to induction of T-helper (Th) type 1 and Treg-type immune responses.
520			_aCONCLUSION: The use of this methylated CpG ODN offers a broad clinical application as a novel therapeutic method for Treg induction and, because of its low cost and small size, should facilitate delivery via nasal, respiratory, gastrointestinal routes, and/or by injection, routes of administration important for vaccine delivery to target sites responsible for respiratory, gastrointestinal, and systemic forms of allergic and autoimmune disease.
520			_aMETHODS: Lymphoproliferative responses of peripheral blood mononuclear cells from four healthy subjects or nine subjects with systemic lupus erythematosus to CT-DNA or phytohemagglutinin (PHA) was measured by tritiated thymidine ([3H]-TdR) incorporation expressed as a stimulation index. Mechanisms of immunosuppressive effects of CT-DNA were evaluated by measurement of the degree of inhibition to lymphoproliferative responses to streptokinase-streptodornase, phytohemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM), or alloantigens by a Con A suppressor assay. The effects of CpG methylation on induction of FoxP3 expression in human T cells were measured by comparing inhibitory responses of synthetic methylated and nonmethylated 8-mer CpG ODN sequences by using cell sorting, in vitro stimulation, and suppressor assay.
520			_aOBJECTIVE: The present study investigated the mechanisms by which calf thymus mammalian double-stranded DNA (CT-DNA) and a synthetic methylated DNA CpG ODN sequence suppress in vitro lymphoproliferative responses to antigens, mitogens, and alloantigens when measured by [3H]-thymidine incorporation and promote FoxP3 expression in human CD4+ T cells in the presence of transforming growth factor (TGF) beta and interleukin-2 (IL-2).
520			_aRESULTS: Here, we showed that CT-DNA and a synthetic methylated DNA 8-mer sequence could suppress antigen-, mitogen-, and alloantigen-induced lymphoproliferation in vitro when measured by [3H]-thymidine. The synthetic methylated DNA CpG ODN but not an unmethylated CpG ODN sequence was shown to promote FoxP3 expression in human CD4+ T cells in the presence of TGF beta and IL-2. The induction of FoxP3+ suppressor cells is dose dependent and offers a potential clinical therapeutic application in allergic and autoimmune and inflammatory diseases.
546			_aEnglish
650			_a*CD4-Positive T-Lymphocytes/im [Immunology]
650			_a*DNA/im [Immunology]
650			_a*Immunotherapy/mt [Methods]
650			_a*Lupus Erythematosus, Systemic/im [Immunology]
650			_a*T-Lymphocytes, Regulatory/im [Immunology]
650			_aAnimals
650			_aCattle
650			_aCell Proliferation
650			_aCells, Cultured
650			_aCpG Islands/ge [Genetics]
650			_aDNA Methylation/im [Immunology]
650			_aDNA/ge [Genetics]
650			_aForkhead Transcription Factors/me [Metabolism]
650			_aHumans
650			_aHypersensitivity/im [Immunology]
650			_aHypersensitivity/th [Therapy]
650			_aImmunosuppression
650			_aIsoantigens/im [Immunology]
650			_aLupus Erythematosus, Systemic/th [Therapy]
650			_aLymphocyte Activation
650			_aTransforming Growth Factor beta/me [Metabolism]
651			_aMedStar Health Research Institute
657			_aJournal Article
700			_aUmans, Jason G
790			_aBellanti JA, Brown ML, Chen W, Lawless OJ, Sandberg K, Umans JG, Wang J, Wang K, Zheng SG, Zhou L
856			_uhttps://dx.doi.org/10.2500/aap.2018.39.4113 _zhttps://dx.doi.org/10.2500/aap.2018.39.4113
942			_cART _dArticle
999			_c3645 _d3645