ライフサイエンスコーパス: central tolerance

1 etion of autoreactive T cells in the thymus (central tolerance).

2 t to rheostat T cell selection and fine-tune central tolerance.

3 l. describe how this may not be a failure of central tolerance.

4 egulator (AIRE) activity and the workings of central tolerance.

5 peripheral tolerance, we proposed to induce central tolerance.

6 cells revise antigen receptors and maintain central tolerance.

7 ory compartment renders B cells resistant to central tolerance.

8 of these TCRs supported an affinity model of central tolerance.

9 whereby autoreactive B cells might "escape" central tolerance.

10 on of diverse self-antigens for establishing central tolerance.

11 Nfkb2(-/-) mice, confirming a key defect in central tolerance.

12 mocytes is essential to the establishment of central tolerance.

13 te by which peripheral DCs may contribute to central tolerance.

14 elic inclusion does not in itself compromise central tolerance.

15 aft rejection, a hallmark of peripheral, not central tolerance.

16 ), which are required for the development of central tolerance.

17 been identified as an important mediator of central tolerance.

18 ve form of MHC class II corrects a defect in central tolerance.

19 autoimmune diseases are caused by failure of central tolerance.

20 er B cell receptor signal and more stringent central tolerance.

21 cytes and thymic stroma that is required for central tolerance.

22 m to affect peripheral tolerance rather than central tolerance.

23 ng distinct types of self-antigens to induce central tolerance.

24 the biology of aging, metabolic syndrome and central tolerance.

25 of aberrant or modified proteins that escape central tolerance.

26 Ags, are essential for the establishment of central tolerance.

27 equired for the induction and maintenance of central tolerance.

28 re essential for the establishment of T cell central tolerance.

29 gens, are essential for the establishment of central tolerance.

30 ells and resulting ability to mediate T cell central tolerance.

31 ritical transcriptional events necessary for central tolerance.

32 n mTECs complements Aire to establish T cell central tolerance.

33 quire blood-borne Ags to induce and maintain central tolerance.

34 of DCs in the thymus substantially enforces central tolerance.

35 ncluding C311Y and C446G, cause breakdown of central tolerance.

36 and CCR7 play distinct or redundant roles in central tolerance.

37 autoimmune regulator (AIRE), a key factor in central tolerance.

38 ciated role for CCR4 in the establishment of central tolerance.

39 GD, probably acting through thymic-dependent central tolerance.

40 lls in the thymus was the major mechanism of central tolerance.

41 ked to defects in apoptosis induction during central tolerance.

42 this phenotype is not caused by a defect in central tolerance.

43 e ATF7ip-MBD1 protein complex in maintaining central tolerance.

44 d promotes differentiation via Erk, breaking central tolerance.

45 m the pool of developing T cells, generating central tolerance.

46 t SLAM/SAP regulate B-cell receptor-mediated central tolerance.

47 s because of AIRE mutation-induced defective central tolerance.

48 cells in the thymus and plays a key role in central tolerance.

49 B cell development that is characteristic of central tolerance.

50 ls with overt autoreactivity is essential to central tolerance.

51 as a failsafe mechanism ensuring appropriate central tolerance.

52 at have escaped the deletional mechanisms of central tolerance.

53 ed architecture inclining to perturbation of central tolerance.

54 character of the immune response and affect central tolerance.

55 be useful in revealing pathways involved in central tolerance.

56 antigen remain within the marrow and undergo central tolerance, a process that revises their antigen

57 ic epithelial cells are essential for T-cell central tolerance, a variety of other traditional APCs a

58 Central tolerance achieved using regimens that eliminate

59 elopmental checkpoints required to establish central tolerance, allowing thymocytes with potentially

60 Our results suggest that central tolerance and attendant L chain receptor editing

61 f the cord blood donor dictate the levels of central tolerance and autoreactive B cells in the periph

62 ely 92 microRNA cluster in regulating B-cell central tolerance and demonstrate that these miRNAs cont

63 virus early in life results in disruption of central tolerance and development of autoimmune disease.

64 The thymus is critical for central tolerance and diverse T-lymphocyte repertoire de

65 The autoreactive T cells that escape central tolerance and form the peripheral self-reactive

66 though CD8alpha+ DCs have been implicated in central tolerance and found to modulate peripheral T cel

67 egulatory T cells (Tregs), are necessary for central tolerance and function as suppressors of autoimm

68 expression in mTECs was sufficient to break central tolerance and induce anti-insulin autoimmunity.

69 largely thought to represent a breakdown in central tolerance and is typically regarded as a harbing

70 se as immunotherapeutics that can circumvent central tolerance and limit graft-versus-host disease.

71 Autoreactive B lymphocytes that escape central tolerance and mature in the periphery are a liab

72 lar and cellular mechanisms mediating thymic central tolerance and prevention of autoimmunity are not

73 (AIRE) is essential for the establishment of central tolerance and prevention of autoimmunity.

74 Anti-insulin B cells escape central tolerance and promote autoimmune diabetes, mimic

75 lishment of immune tolerance, including both central tolerance and the peripheral function of regulat

76 development is required to establish T-cell central tolerance and to generate naive T cells, both of

77 ion of T regulatory cells, playing a role in central tolerance and tumor immunity.

78 tion of self-reactive T cells in the thymus (central tolerance) and the regulation of tolerance in ma

79 , the distinct roles of thymic DC subsets in central tolerance, and age-associated changes in thymic

80 pable of inducing diabetes can escape normal central tolerance, and can cause T1DM if left unchecked.

81 AIRE) gene contributes to the maintenance of central tolerance, and complete loss of AIRE function re

82 self-antigens in the thymus, exhibit reduced central tolerance, and develop a spontaneous, chronic, a

83 ) said antigens are not perfectly covered by central tolerance (antigenicity), (2) cell death occurs

84 Aire-controlled mechanisms of central tolerance are largely dispensable in the adult,

85 driven autoimmune disease caused by impaired central tolerance, are susceptible to chronic fungal inf

86 p APECED-like phenotypes, including impaired central tolerance, autoreactive T cells, chronic fungal

87 ar syndrome type I, called AIRE, has brought central tolerance back into focus as an important mechan

88 his transcriptional control element promotes central tolerance both by furnishing a specific thymic s

89 hich not only contribute to the induction of central tolerance, but also regulate the homeostasis of

90 in escape of PLP 139-151 reactive cells from central tolerance, but is due to expression of a splice

91 BCR-transgenic mice, Sle2(z) did not breach central tolerance, but it led to heightened expression o

92 icted antigens (TRA) to thymocytes to induce central tolerance, but the relative contributions of the

93 bound autoantigens can bypass mechanisms of central tolerance by coexpressing nonautoreactive Abs.

94 ire of VH125Tg/NOD mice, suggesting enhanced central tolerance by direct BCR interaction.

95 xpressing a particular Vkappa L chain, evade central tolerance by down-regulating BCR levels.

96 hus, CMV-vectored cancer vaccines can bypass central tolerance by eliciting T cells to noncanonical e

97 ne regulator (Aire) plays a critical role in central tolerance by promoting the display of tissue-spe

98 ne regulator (Aire) plays a critical role in central tolerance by promoting thymic expression of self

99 B cell numbers, suggesting that escape from central tolerance by receptor editing from one IgH allel

100 ace" in the recipient thymus so that lasting central tolerance can be achieved.

101 obust allogeneic hematopoietic chimerism and central tolerance can be established in the absence of h

102 Central tolerance can be mediated by peripheral dendriti

103 indicate that weak or faulty checkpoints for central tolerance can be overcome by autoantigen-specifi

104 Thus, our studies demonstrated that central tolerance can paradoxically result in systemic a

105 ic protein-coding mutations, are exempt from central tolerance, can generate robust immune responses(

106 eping with the contribution of thymic DCs to central tolerance, CCR4 is involved in regulating negati

107 ent during competitive reconstitution at the central tolerance checkpoint.

108 These autoreactive B cells can evade central tolerance checkpoints and migrate to the periphe

109 Thus, escape from central tolerance, combined with peripheral expansion by

110 dritic cells (DCs) are critical mediators of central tolerance, cooperating with medullary thymic epi

111 Combined with their role as mediators of central tolerance, DCs are thus poised to provide homeos

112 Our results identify permissive central tolerance, defective peripheral tolerance, and a

113 systems, because both fail to manifest clear central tolerance defects, but they nevertheless promote

114 e data suggest that 1) medulla formation and central tolerance depend on activating the alternative N

115 The extent of central tolerance depends on the diversity of self-pepti

116 Central tolerance depends upon Ag-mediated cell death in

117 ve in thymic expression of self antigens and central tolerance, develop spontaneous prostatitis.

118 To establish central tolerance, developing T cells must enter the thy

119 CCR4 is poised to contribute to central tolerance due to its expression by post-positive

120 TECs) play an essential role in establishing central tolerance due to their unique capacity to presen

121 heral lymphoid organs after establishment of central tolerance during B cell development.

122 ls specific for these antigens is limited by central tolerance during T-cell development in the thymu

123 Thymic central tolerance eliminates most immature T cells with

124 for mature autoreactive B cells that escape central tolerance enforced by receptor editing and clona

125 Our analysis indicates that central tolerance enhances the efficiency of peripheral

126 Central tolerance ensures autoreactive T cells are elimi

127 likely impact the efficiency and quality of central tolerance established over the lifespan.

128 ta suggest that it is not necessary to break central tolerance, even in an autoimmune mouse, to gener

129 ne regulator (Aire), a critical regulator of central tolerance expressed by medullary thymic epitheli

130 toimmune regulator Aire is a key mediator of central tolerance for peripherally restricted antigens.

131 ent progress surrounding the role of Aire in central tolerance from a molecular, genetic and developm

132 usion enables autoreactive B cells to bypass central tolerance giving rise to B cells that retain dan

133 LT in thymic Ag processing and generation of central tolerance has not been investigated.

134 With the discovery of AIRE, central tolerance has re-emerged as a crucial check agai

135 llogeneic hematopoietic chimerism leading to central tolerance has significant therapeutic potential.

136 nal deletion is considered a major driver of central tolerance; however, other mechanisms such as ind

137 toire selection in the thymus and control of central tolerance, (iii) it plays a role in T and B cell

138 To analyze B lymphocyte central tolerance in a polyclonal immune system, mice we

139 Most MBP-specific T cells are eliminated by central tolerance in adult mice, however, the developmen

140 isease process and demonstrated a failure in central tolerance in aire-deficient mice.

141 plays an important role in the regulation of central tolerance in an Aire-dependent manner.

142 Peripheral B cell tolerance differs from central tolerance in anatomic location, in the stage of

143 rtant implications on the breaking of B cell central tolerance in autoimmunity.

144 ies a critical role for PD-1 in establishing central tolerance in autoreactive T cells that escape cl

145 lymorphisms of Ly108 in mice strongly impact central tolerance in both B and T cell development, pred

146 Impaired central tolerance in NOD mice was most prominent in a po

147 Our data support a role for AID in B cell central tolerance in preventing the expansion of autorea

148 eactive B lymphocytes that are not culled by central tolerance in the bone marrow frequently enter th

149 macrophages, are essential for establishing central tolerance in the thymus by promoting T cell clon

150 Central tolerance in the thymus ensures that the develop

151 ilization of the NF-kappaB system to promote central tolerance in the thymus, in apparent contrast wi

152 ates the transcription of genes that control central tolerance in the thymus.

153 (mTEC(hi)) are critical for the induction of central tolerance in the thymus.

154 critical transcription factor for generating central tolerance in the thymus.

155 PTM) of islet autoantigens can cause lack of central tolerance in type 1 diabetes (T1D).

156 localization and support a revised model of central tolerance in which CCR4 and CCR7 promote early a

157 hlight the importance of thymically imposed "central" tolerance in controlling autoimmunity.

158 he fundamental role of AIRE and pGE, namely, central tolerance, in the predisposition to autoimmunity

159 Efficient mechanisms of central tolerance, including receptor editing and deleti

160 ance, Bcl-2 overexpression failed to inhibit central tolerance induced by bone marrow antigen express

161 Finally, in a model of central tolerance induced by mixed allogeneic chimerism,

162 e report that aGVHD weakens the platform for central tolerance induction because individual TRAs are

163 , the effects of bone marrow transduction on central tolerance induction was demonstrated by the prog

164 e-mediated regulation of gene expression and central tolerance induction, but this influence is unlik

165 ype is influenced by an additional defect in central tolerance induction, generated by either crossin

166 e operation of any individual Aire(+) MEC in central tolerance induction.

167 t the lymphotoxin pathway may play a role in central tolerance induction.

168 ing high-affinity, autoreactive T cells from central tolerance induction.

169 altering B cell development, selection, and central tolerance induction.

170 pic TRA repertoire, weakens the platform for central tolerance induction.

171 y thymic epithelial cells, a key process for central tolerance induction.

172 anscriptome and so was crucial for effective central tolerance induction.

173 eve promiscuous gene expression required for central tolerance induction.

174 Ac1-9 itself can be an effective inducer of central tolerance induction; however, in the context of

175 Thymic central tolerance is a critical process that prevents au

176 B cell central tolerance is a process through which self-reacti

177 e selection and demonstrate that a defect in central tolerance is a putative mechanism by which COPA

178 Central tolerance is an essential process that protects

179 They suggest that once central tolerance is bypassed, autoreactive cells arrivi

180 T-cell central tolerance is controlled by thymocyte TCR recogni

181 Central tolerance is dependent on the intrathymic expres

182 Thymic central tolerance is essential to preventing autoimmunit

183 How organ-specific central tolerance is established and regulated has been

184 In Aire-deficient humans or mice, central tolerance is incomplete and multiorgan autoimmun

185 Moreover, their role in central tolerance is obscured by redundancy among the Nr

186 Effective central tolerance is required to control the large exten

187 further proposed that a similar mechanism of central tolerance is responsible for the immunotolerance

188 sults from our study suggest that defects in central tolerance may contribute to SS and provide a new

189 toire can be salvaged by receptor editing, a central tolerance mechanism that alters BCR specificity

190 normal circulating human B cells that escape central tolerance mechanisms and express self-reactive a

191 ating that complement receptors appear after central tolerance mechanisms are completed.

192 However, an important role for central tolerance mechanisms has been reemphasized by re

193 Together with damage to central tolerance mechanisms in the thymus, these findin

194 Central tolerance mechanisms involve medullary thymic ep

195 ing of the interplay between these different central tolerance mechanisms is still lacking.

196 rus in its natural host species suggest that central tolerance mechanisms prune the protective antivi

197 e B cells bearing 2F5 chimeric antibodies to central tolerance mechanisms.

198 We show that MBP-specific T cells undergo central tolerance mediated by bone marrow-derived antige

199 ations of autoimmune regulator (AIRE), a key central tolerance mediator, leading to abnormal autoreac

200 presented that NOD mice display a defect in central tolerance (negative selection) of thymocytes.

201 They find that Aire influences central tolerance not only by promoting the expression o

202 GAD65 reflects at minimum a basic defect in central tolerance, not seen in animals not predisposed t

203 and CCR7 promote medullary accumulation and central tolerance of distinct post-positive selection th

204 Here we show that central tolerance of MHC class I-restricted T cells spec

205 lary epithelial cells (MECs) is critical for central tolerance of self.

206 e expression systems as a strategy to bypass central tolerance, offering a path toward durable, self-

207 e selection, while medullary (m) TECs impose central tolerance on the T cell repertoire.

208 b-based tolerance regimen that relies on the central tolerance pathway.

209 nd nonlymphoid tissues regulates DC-mediated central tolerance, peripheral T cell homeostasis, and in

210 n NOD mice and suggest that dysregulation of central tolerance permits their escape into the peripher

211 The central tolerance phenotype implies that tolerizing self

212 Central tolerance plays a critical role in eliminating s

213 These findings suggest that Aire-dependent central tolerance plays a critical role in maintaining m

214 Central tolerance plays a significant role in preventing

215 Central tolerance prevents autoimmunity, but also limits

216 f self-antigen presented in the thymus, this central tolerance process is often incomplete, and addit

217 on machinery in the thymus and a perceptible central tolerance process.

218 ate a novel role for TLR9 signal strength in central tolerance, providing insight into the interplay

219 er one alone, led to a profound breakdown in central tolerance resulting in rapid and fatal multiorga

220 checkpoints: a more stringent selection for central tolerance, resulting in reduced numbers of autor

221 M14, high affinity RF B cells are subject to central tolerance, showing that there is not an absolute

222 Since they are not covered by central tolerance, such tumor neoantigens (TNAs) should

223 that this may compensate for deficiencies in central tolerance that occur owing to thymic involution.

224 ity in the bone marrow undergo mechanisms of central tolerance that prevent their entry into the peri

225 These results indicate that modulating central tolerance through RANKL can alter thymic output

226 As one of the biological foundations of central tolerance, thymic tissue carries with it the abi

227 To undergo central tolerance, thymocytes must enter the medulla to

228 f prolonging gene expression by induction of central tolerance to adenoviral antigens in bilirubin-UD

229 d potentially carry with it the induction of central tolerance to any other organ or tissue from the

230 ollagen (CII) in mTECs and the corresponding central tolerance to CII are AIRE independent but lympho

231 cted in host T cells in chimeras, suggesting central tolerance to donor alloantigens.

232 , given its immunogenicity, we asked whether central tolerance to donor major histocompatibility comp

233 might synergize with subclinical defects in central tolerance to elicit autoimmune disease.

234 elf-tolerant system must have a mechanism of central tolerance to ensure that self-reactive T cells a

235 However, in the presence of a reduced central tolerance to FTCD, a strong regulatory T-cell re

236 a congenital absence of FVIII do not develop central tolerance to FVIII, and therefore, any control o

237 mmune encephalomyelitis severity by limiting central tolerance to myelin oligodendrocyte glycoprotein

238 indings suggest that defective Aire-mediated central tolerance to myelin protein zero initiates an au

239 Central tolerance to proinsulin in transgenic NOD mice w

240 Our findings show that central tolerance to retinal and pancreatic Ags is quali

241 mic epithelial cells in T cell selection and central tolerance to some autoantigens.

242 differentiation and prevent the emergence of central tolerance to the invading pathogens.

243 To study central tolerance to the major product of ongoing apopto

244 ed at least in part by capacity to establish central tolerance to the relevant autoantigen.

245 Central tolerance to these antigens is incomplete, yet n

246 These results indicate that central tolerance to this encephalitogenic MBP epitope m

247 Mtecs express a given TSA, it was unclear if central tolerance to TSA was induced directly by Mtec an

248 -Langerin-2.5HIP delivery can enhance T-cell central tolerance toward cognate thymocytes in NOD.BDC2.

249 Central tolerance toward tissue-restricted Ags is consid

250 litates escape of TSHR-reactive T cells from central tolerance, triggering GD.

251 Central tolerance was induced in C57BL/10J mdx (dystroph

252 Central tolerance was undetectable until 10 weeks and co

253 el in which all human Igk(+) B cells undergo central tolerance, we discovered that human autoreactive

254 ontribution of the NOD genetic background to central tolerance, we followed the behavior of BDC2.5 cl

255 eement with a B cell-intrinsic regulation of central tolerance, we identified SAP expression in a dis

256 The actions of mAb123 on central tolerance were also investigated, because select

257 Deletion has been implicated in central tolerance, whereas peripheral tolerance has gene

258 T-cell responses are normally restrained by central tolerance, which may be relevant to understandin

259 igens can require approaches that circumvent central tolerance, which may increase the risk of cross-

260 -deficient mice have largely been deleted by central tolerance, while the same T cells in WT mice are

261 marrow leads to hematopoietic chimerism and central tolerance with no myeloablation and no GVHD.