Abstract:
BACKGROUND: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. OBJECTIVE: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). METHODS: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. RESULTS: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. CONCLUSION: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.
journal_name
Allergy Asthma Procjournal_title
Allergy and asthma proceedingsauthors
Lawless OJ,Bellanti JA,Brown ML,Sandberg K,Umans JG,Zhou L,Chen W,Wang J,Wang K,Zheng SGdoi
10.2500/aap.2018.39.4113subject
Has Abstractpub_date
2018-03-01 00:00:00pages
143-152issue
2eissn
1088-5412issn
1539-6304journal_volume
39pub_type
杂志文章abstract::Diagnosis of tuberculosis (TB) in children by the tuberculin skin test (TST) poses a diagnostic challenge for physicians due to its low specificity and cross-reactivity with nontuberculous mycobacteria and bacille Calmette-Guerin (BCG). Although interferon-gamma release assays (IGRAs) have been shown as novel TST alte...
journal_title:Allergy and asthma proceedings
pub_type: 杂志文章
doi:10.2500/aap.2012.33.3574
更新日期:2012-05-01 00:00:00
abstract::Background: The European Academy of Allergy and Clinical Immunology guidelines, strongly recommended allergen immunotherapy (AIT) as an effective treatment to achieve long-term clinical benefits and to modify the natural history of allergic diseases. Sublingual immunotherapy (SLIT) offers the possibility of home admin...
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pub_type: 杂志文章
doi:10.2500/aap.2020.41.200063
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journal_title:Allergy and asthma proceedings
pub_type: 杂志文章
doi:10.2500/aap.2014.35.3777
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doi:10.2500/aap.2008.29.3145
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journal_title:Allergy and asthma proceedings
pub_type: 杂志文章,随机对照试验
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更新日期:2012-09-01 00:00:00
abstract::Eotaxin is the major eosinophil chemoattractant found in bronchoalveolar lavage (BAL) fluid from sensitized guinea pigs after antigen challenge. In this study we have performed immunostaining for eotaxin in airways obtained from challenged animals and examined purified guinea pig lung cells (epithelial cells > 98% pur...
journal_title:Allergy and asthma proceedings
pub_type: 杂志文章
doi:10.2500/108854198778557926
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journal_title:Allergy and asthma proceedings
pub_type: 杂志文章
doi:10.2500/aap.2011.32.3519
更新日期:2012-01-01 00:00:00
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journal_title:Allergy and asthma proceedings
pub_type: 杂志文章
doi:
更新日期:2005-01-01 00:00:00
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pub_type: 杂志文章,随机对照试验
doi:10.2500/aap2007.28.3033
更新日期:2007-09-01 00:00:00
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journal_title:Allergy and asthma proceedings
pub_type: 杂志文章,评审
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journal_title:Allergy and asthma proceedings
pub_type: 杂志文章,评审
doi:10.2500/aap.2006.27.2871
更新日期:2006-07-01 00:00:00
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journal_title:Allergy and asthma proceedings
pub_type: 杂志文章
doi:10.2500/aap.2018.39.4135
更新日期:2018-07-01 00:00:00
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journal_title:Allergy and asthma proceedings
pub_type: 杂志文章,评审
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更新日期:2013-01-01 00:00:00
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journal_title:Allergy and asthma proceedings
pub_type: 杂志文章
doi:10.2500/108854198778557845
更新日期:1998-07-01 00:00:00
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pub_type: 杂志文章
doi:10.2500/aap.2017.38.4009
更新日期:2017-01-01 00:00:00
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journal_title:Allergy and asthma proceedings
pub_type: 杂志文章,评审
doi:10.2500/aap.2012.33.3537
更新日期:2012-05-01 00:00:00
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journal_title:Allergy and asthma proceedings
pub_type: 杂志文章
doi:10.2500/aap.2014.35.3751
更新日期:2014-05-01 00:00:00
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journal_title:Allergy and asthma proceedings
pub_type: 杂志文章
doi:
更新日期:2001-11-01 00:00:00
abstract::Outcomes research is becoming an integral part of the sweeping changes occurring in the U.S. health care system. By developing outcomes monitoring systems in allergic disorders, allergists will be able to collect information showing their commitment to excellent clinical care, which improves the patient's quality of l...
journal_title:Allergy and asthma proceedings
pub_type: 杂志文章,评审
doi:10.2500/108854196778606455
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pub_type: 信件
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更新日期:2019-05-01 00:00:00
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journal_title:Allergy and asthma proceedings
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:2002-09-01 00:00:00
abstract::Background: Approximately 80% of patients with asthma and chronic obstructive pulmonary disease incorrectly use a metered-dose inhaler and, therefore, fail to obtain full benefit from their inhaler medication. Beclomethasone dipropionate (BDP) hydrofluoroalkane, an inhalation aerosol administered via a breath-actuated...
journal_title:Allergy and asthma proceedings
pub_type: 杂志文章
doi:10.2500/aap.2019.40.4215
更新日期:2019-05-01 00:00:00
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journal_title:Allergy and asthma proceedings
pub_type: 杂志文章
doi:10.2500/aap.2008.29.3174
更新日期:2008-11-01 00:00:00
abstract::Food-dependent, exercise-induced anaphylaxis (FDEIA) is a clinically distinct form of anaphylaxis in which symptoms occur only when the patient exercises within a few hours of eating the food. Its precise mechanism remains unclear and has been reported to have a wide spectrum of presentations. The objective of this re...
journal_title:Allergy and asthma proceedings
pub_type: 杂志文章
doi:10.2500/aap.2007.28.2951
更新日期:2007-01-01 00:00:00
abstract::Background: The majority of patients for elective surgery and with a history of penicillin allergy are placed on alternative prophylactic antibiotic therapies, which have been associated with the emergence of multidrug-resistant pathogens and increased morbidity and mortality rates. However, self-reporting of penicill...
journal_title:Allergy and asthma proceedings
pub_type: 杂志文章,meta分析
doi:10.2500/aap.2018.39.4178
更新日期:2018-11-01 00:00:00
abstract::Immediate-hypersensitivity reactions related to latex products have increased rapidly in recent years. However, a reliable diagnosis is hampered by lack of purified and well characterized latex allergens. We have purified allergens in natural rubber latex (NRL) after SDS-PAGE by electroelution, and tested specific IgE...
journal_title:Allergy and asthma proceedings
pub_type: 杂志文章
doi:10.2500/108854196778996921
更新日期:1996-07-01 00:00:00
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journal_title:Allergy and asthma proceedings
pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2016-09-01 00:00:00
abstract::Immunotherapy can be administered either sublingually (sublingual immunotherapy [SLIT]) or subcutaneously (subcutaneous immunotherapy [SCIT]). The rate of route switching, required by patients, can provide an indirect evaluation of patients' preferences and adherence. The authors retrospectively reviewed patients' fil...
journal_title:Allergy and asthma proceedings
pub_type: 杂志文章
doi:10.2500/aap.2013.34.3696
更新日期:2013-11-01 00:00:00
abstract::Suboptimal asthma control may be caused by a combination of factors, such as nonadherence to guidelines, lack of compliance, and poor asthma education. The aim was to assess patients' knowledge of asthma and different management strategies, including patients' attitudes toward involvement in treatment decisions. The p...
journal_title:Allergy and asthma proceedings
pub_type: 杂志文章
doi:10.2500/aap.2007.28.3001
更新日期:2007-05-01 00:00:00