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 m to affect peripheral tolerance rather than central tolerance.

3 cells revise antigen receptors and maintain central tolerance.

4 ory compartment renders B cells resistant to central tolerance.

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

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

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

8 mocytes is essential to the establishment of central tolerance.

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

10 elic inclusion does not in itself compromise central tolerance.

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

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

13 been identified as an important mediator of central tolerance.

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

15 autoimmune diseases are caused by failure of central tolerance.

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

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

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

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

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

21 ked to defects in apoptosis induction during central tolerance.

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

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

24 equired for the induction and maintenance of central tolerance.

25 d promotes differentiation via Erk, breaking central tolerance.

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

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

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

29 B cell development that is characteristic of central tolerance.

30 ls with overt autoreactivity is essential to central tolerance.

31 as a failsafe mechanism ensuring appropriate central tolerance.

32 at have escaped the deletional mechanisms of central tolerance.

33 character of the immune response and affect central tolerance.

34 be useful in revealing pathways involved in central tolerance.

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

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

37 peripheral tolerance, we proposed to induce central tolerance.

38 Central tolerance achieved using regimens that eliminate

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

68 Central tolerance can be mediated by peripheral dendriti

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

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

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

72 ent during competitive reconstitution at the central tolerance checkpoint.

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

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

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

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

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

78 Central tolerance depends upon Ag-mediated cell death in

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

121 eve promiscuous gene expression required for central tolerance induction.

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

123 Thymic central tolerance is a critical process that prevents au

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

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

126 Central tolerance is dependent on the intrathymic expres

127 Thymic central tolerance is essential to preventing autoimmunit

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

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

130 Effective central tolerance is required to control the large exten

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

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

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

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

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

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

137 Central tolerance mechanisms involve medullary thymic ep

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

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

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

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

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

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

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

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

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

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

148 The central tolerance phenotype implies that tolerizing self

149 Central tolerance plays a critical role in eliminating s

150 Central tolerance plays a significant role in preventing

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

168 Central tolerance to proinsulin in transgenic NOD mice w

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

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

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

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

173 Central tolerance to these antigens is incomplete, yet n

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

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

176 Central tolerance toward tissue-restricted Ags is consid

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

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

179 Central tolerance was undetectable until 10 weeks and co

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

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

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

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

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

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

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