ライフサイエンスコーパス: self-reactive

1 that disease-associated IgG4 antibodies are self-reactive.

2 cleobase substrates in this approach are not self-reactive, a base-filling approach may reduce the fo

3 e of the CNS that is mediated, in part, by a self-reactive Ab against the astrocyte aquaporin-4 prote

4 sent a higher serum level of natural Igs and self-reactive Abs.

5 CD25(hi) (Triple(hi)) Treg cells were highly self-reactive and controlled lympho-proliferation in per

6 BV(+) memory B cells express lower levels of self-reactive and especially polyreactive antibodies tha

7 o)CD25(lo) (Triple(lo)) Treg cells were less self-reactive and limited the development of colitis by

8 ction of IgG-positive memory B cells express self-reactive and polyreactive IgG antibodies that frequ

9 Self-reactive antibodies and parasite-specific IgG in fe

10 t mice produced high amounts of low-affinity self-reactive antibodies and showed significant lymphocy

11 ntibody self/non-self discrimination discard self-reactive antibodies before they can be tested for b

12 In systemic lupus erythematosus (SLE), self-reactive antibodies can target the kidney (lupus ne

13 The occurrence of self-reactive antibodies correlated with overall antibod

14 of aberrant Tfh cells and the generation of self-reactive antibodies in experimental murine lupus, b

15 0) is an autoimmune disease characterized by self-reactive antibodies resulting in systemic inflammat

16 ferentiation and enhancing the production of self-reactive antibodies that cause lupus-like nephritis

17 nondonor HLA specific antibodies (NDSA) and self-reactive antibodies that develop alongside donor-sp

18 gene segment encodes in humans intrinsically self-reactive antibodies that recognize I/i carbohydrate

19 However, in females, the presence of self-reactive antibodies was positively associated with

20 pid response that includes the production of self-reactive antibodies.

21 t and thus is not involved in the editing of self-reactive antibodies.

22 d associations between fitness and heritable self-reactive antibody responsiveness in a wild populati

23 Endogenous self-reactive autoantibodies (AAs) recognize a range of

24 Yet, not everyone who developes self-reactive autoantibodies will manifest autoimmune di

25 ls, we have limited mechanistic insight into self-reactive autoimmune T cell development and their es

26 in suppressing the spontaneous activation of self-reactive B and T cells during lupus.

27 in T cells prevented Tfh cell accumulation, self-reactive B cell activation, and autoantibody produc

28 lator), a cytokine that promotes survival of self-reactive B cell clones.

29 ition on self-antigens may serve to activate self-reactive B cell clones.

30 B cell follicles to prevent the expansion of self-reactive B cell clones.

31 eceptor editing and deletion, prevent highly self-reactive B cell receptors (BCRs) from populating th

32 These results support the generation of self-reactive B cell repertoires during the autoimmune p

33 a provide insight into the maturation of the self-reactive B cell response, contextualizing the epito

34 chanisms limit the expansion and function of self-reactive B cells activated under these conditions.

35 important role of Act1 in the regulation of self-reactive B cells and reveal how Act1 functions to p

36 ngage a deletional checkpoint for removal of self-reactive B cells and selectively kill ALL cells.

37 Some self-reactive B cells are able to escape these checkpoin

38 Self-reactive B cells are generally removed by receptor

39 We show that although self-reactive B cells are recruited into the germinal ce

40 r editing is important for understanding how self-reactive B cells are regulated.

41 central tolerance is a process through which self-reactive B cells are removed from the B cell repert

42 In particular, how self-reactive B cells are restrained during bystander in

43 t help to distinguish self-reactive from non-self-reactive B cells at four distinct checkpoints.

44 ed on FDCs mediates effective elimination of self-reactive B cells at the transitional stage.

45 However, selection of self-reactive B cells by Ag on FDCs has not been address

46 tible genetic backgrounds with the rescue of self-reactive B cells by T cells allows the generation o

47 However, our understanding of how self-reactive B cells escape self-tolerance checkpoints

48 ing heterozygous Pik3cd activating mutation, self-reactive B cells exhibit a cell-autonomous subversi

49 inal centers (GCs) in lymphoid tissues where self-reactive B cells expand and differentiate.

50 Checkpoints are in place to prevent self-reactive B cells from further development and activ

51 Pathogenic autoantibodies, arising from self-reactive B cells having undergone somatic hypermuta

52 s of layered peripheral checkpoints maintain self-reactive B cells in an unresponsive state.

53 Self-reactive B cells in BALB/c AM14 transgenic (Tg) rhe

54 We thus propose that Nur77 is upregulated in self-reactive B cells in response to chronic Ag stimulat

55 Although the negative selection of self-reactive B cells in the bone marrow of mammals has

56 y results in the progressive accumulation of self-reactive B cells in the mature repertoire with age

57 a role for Nur77 in restraining survival of self-reactive B cells in the periphery under conditions

58 lts may explain how persistent activation of self-reactive B cells induces the development of autoimm

59 Self-reactive B cells not controlled by receptor editing

60 Notwithstanding, some self-reactive B cells persist beyond this checkpoint, sh

61 e mechanisms that prevent the development of self-reactive B cells remain incompletely understood.

62 clones were newly generated B cells and not self-reactive B cells that had escaped depletion and rep

63 competent peripheral B cell pool limited in self-reactive B cells that may produce pathogenic autoan

64 MYD88(L265P) caused self-reactive B cells to accumulate in vivo only when ap

65 ormally occurs following chronic exposure of self-reactive B cells to self-antigen, did not take plac

66 results in B cell hyperactivity, survival of self-reactive B cells, and differentiation to autoantibo

67 repression of CD86 on chronically stimulated self-reactive B cells, which contributes, at least in pa

68 n FDCs and to monitor the fate of developing self-reactive B cells.

69 s a critical physiologic mechanism to sensor self-reactive B cells.

70 efective B cell selection and elimination of self-reactive B cells.

71 e generation, activation, and persistence of self-reactive B cells.

72 ar to be less frequently used to edit/revise self-reactive B cells.

73 orchestrating secondary Ig rearrangements in self-reactive B cells.

74 s critical for suppressing the activation of self-reactive B cells; however, the mechanism underlying

75 ment and subsequent long-term maintenance of self-reactive B-1 B cells.

76 In mice, neonatally-developing, self-reactive B-1 cells generate steady levels of natura

77 tionally equivalent to acute activation of a self-reactive BCR on ALL cells.

78 inflammation was lost on expression of a non-self-reactive BCR or loss of MyD88 in Ikaros-deficient B

79 cells upon acquisition of a B1 cell-typical self-reactive BCR through a phase of proliferative expan

80 B cells from elimination by diluting out the self-reactive BCR through the expression of a second inn

81 hyperactivation above maximum (for example, self-reactive BCR) thresholds of signalling strength cau

82 a response to inappropriate signaling from a self-reactive BCR, or as part of a stochastic mechanism

83 Dysregulation of CSR can cause self-reactive BCRs and B cell lymphomas; understanding t

84 onfunctional IgH genes or IgH genes encoding self-reactive BCRs and contributes to the diversificatio

85 figuration, express low-affinity, poly-, and self-reactive BCRs.

86 e B-cell receptor (BCR) repertoire including self-reactive BCRs.

87 can be induced from pre-existing, residual, self-reactive BnAb-expressing B cells in vivo using a st

88 The inappropriate expansion of self-reactive "bystander" T cells can contribute to auto

89 a-light-chain+ naive B cells, development of self-reactive CD11c+FAS+ B cells, and evidence for spont

90 ted by MHC class II molecules and shapes the self-reactive CD4 T cell repertoire.

91 Self-reactive CD4 T cells are thought to have a central

92 ht into the role of TSSP in the selection of self-reactive CD4 T cells by endogenous self-Ags, we exa

93 d the elaborate Treg-dependent regulation of self-reactive CD4(+) T cell proliferation within the CNS

94 Self-reactive CD4(+) T cells are major drivers of autoim

95 Furthermore, self-reactive CD4(+) T cells that expanded in the presen

96 the induction and progression of TnI-AM when self-reactive CD4(+) T cells were primed.

97 ognition of systemic Ag induces tolerance in self-reactive CD4(+) T cells, but induction of CD40 sign

98 gning immunotherapies that incorporate tumor/self-reactive CD4(+) T cells.

99 reby reducing the boost for the expansion of self-reactive CD4(+) T cells.

100 Of interest, the self-reactive CD4(+) Tconvs and Tregs displayed overlapp

101 of acquired TTP by stimulating low-affinity, self-reactive CD4+ T cells.

102 subsets revealed that IL-2 was expressed in self-reactive CD4SP thymocytes, which also contain T reg

103 led by a key niche factor, IL-2, produced by self-reactive CD4SP thymocytes.

104 We also show that DN T cells derived from self-reactive CD8 cells express the inhibitory molecules

105 To explore whether self-reactive CD8 T cells could attack CNS neurons in vi

106 This work reveals the complex regulation of self-reactive CD8 T cells in vitiligo and demonstrates t

107 nity by inducing MHC-I-dependent deletion of self-reactive CD8(+) T cells and MHC-II-dependent anergy

108 There is compelling evidence that self-reactive CD8(+) T cells are a major factor in devel

109 lls (LNSCs), have been described to tolerize self-reactive CD8(+) T cells in LNs.

110 rcumvent this problem, and given the role of self-reactive CD8(+) T cells in the development of type

111 B cells engage self-reactive CD8(+) T cells in the pancreatic lymph nod

112 associated epigenetic programs revealed that self-reactive CD8(+) T cells isolated from murine lympho

113 conditions like type 1 diabetes to progress, self-reactive CD8(+) T cells would need to interact with

114 levant specificity, blunted the expansion of self-reactive CD8(+) T cells, suggesting B-cell antigen

115 diabetes by cross-presenting autoantigen to self-reactive CD8(+) T cells.

116 n provokes the generation of DN T cells from self-reactive CD8(+) T cells.

117 T cells to adopt the phenotype of their less self-reactive cell-counterparts.

118 hen CD8 T cells from repertoires enriched in self-reactive cells (Aire-deficient) are transferred int

119 in a specialized organ, the thymus, in which self-reactive cells are either eliminated or differentia

120 The self-reactive cells initially exhibited effector activit

121 oreactive heavy chain, we show enrichment in self-reactive cells specifically at the transitional to

122 particles (NPs) to restore Treg control over self-reactive cells, aiming to achieve long-term disease

123 the expression of PD-1 and Helios, represent self-reactive cells.

124 toll in the form of pathologies mediated by self-reactive cells.

125 is purged of a substantial portion of highly self-reactive cells.

126 ty, immunological memory, and elimination of self-reactive clones (2).

127 -1(+) IELp population included more strongly self-reactive clones and was largely restricted by class

128 rs, we examined the defective elimination of self-reactive clones in Aire-deficient mice.

129 vides the evidence that complete deletion of self-reactive clones is rare.

130 e B cells from WAS patients were enriched in self-reactive clones, revealing that peripheral B cell t

131 a substantial proportion of polyreactive and self-reactive clonotypes, suggesting that activation che

132 ) use a distinct TCR repertoire and are more self-reactive compared with conventional T cells.

133 taneous T cell activation but instead causes self-reactive Ctla4(-/-) T cells to accumulate in second

134 ulatory pathway regulates the trafficking of self-reactive Ctla4(-/-) T cells to tissues.

135 ovel mechanism that prevents accumulation of self-reactive cytotoxic effectors, highlighting the impo

136 esponses by CD4(+) T cells, likely driving a self-reactive disease process.

137 during acute GVHD leads to the emergence of self-reactive donor T cells that are capable of recogniz

138 B7-1 pathway inhibits potentially pathogenic self-reactive effector CD4(+) and CD8(+) T cell response

139 ntal role in immune tolerance via control of self-reactive effector T cells (Teffs).

140 ore, FMNL1-deficiency impairs the ability of self-reactive effector T cells to induce autoimmune dise

141 maintain peripheral tolerance by suppressing self-reactive effector T cells.

142 o protect the organism against autoimmunity, self-reactive effector/memory T cells (T(E/M)) are contr

143 hat the T cell repertoire is in fact broadly self-reactive, even self-centered.

144 , or apoptosis, and that help to distinguish self-reactive from non-self-reactive B cells at four dis

145 e through failure of FAS-mediated removal of self-reactive germinal center (GC) B cells.

146 lls is associated with positive selection of self-reactive germinal center B cells and autoimmunity i

147 These data suggest that poly- and self-reactive germline antibodies such as TLF2-associate

148 Using a biomarker to track a self-reactive H chain in peripheral blood, we found evid

149 that can be used to predict whether TCRs are self-reactive have not been fully elucidated.

150 By following the fate of self-reactive human kappa(+) B cells relative to nonauto

151 recent reports describing the prevalence of self-reactive IgE and discuss novel findings that incrim

152 The presence of circulating self-reactive IgE in patients with autoimmune disorders

153 Collectively, these results indicate that self-reactive IgE is produced during malaria.

154 , the negative correlation between levels of self-reactive IgE to 14-3-3 epsilon protein and parasite

155 duals with SLE also have elevated serum IgE, self-reactive IgEs and activated basophils that express

156 The presence of self-reactive IgG autoantibodies in human sera is largel

157 In normal mice, self-reactive IgG2a-switched B cells were deleted, leadi

158 Self-reactive IgGs contribute to the pathology of autoim

159 We investigate the role of self-reactive IgM in the unique setting of transplantati

160 y-deficient mice reconstituted with specific self-reactive IgM monoclonal antibodies, we identified n

161 sis patients also contained polyreactive and self-reactive IgM.

162 undamental and unanticipated role in purging self-reactive immature and transitional B cells during t

163 hrough its RAG-coupled genotoxic activity in self-reactive immature B cells.

164 ent in the thymus, deletion of high-affinity self-reactive immature thymocytes contributes to toleran

165 y regulated to generate protective but limit self-reactive immune responses.

166 on of T(FR) cells also resulted in increased self-reactive immunoglobulin (Ig) G and IgE.

167 ing Ab (bnAb) 2F5 has been shown to be poly-/self-reactive in vitro, and we previously demonstrated t

168 e repertoire contains potentially beneficial self-reactive innate-like B cell specificities that may

169 Self-reactive, innate-like B cells contact and are selec

170 es may be caused, in part, by low numbers of self-reactive lymphocytes surviving negative selection.

171 -invariant natural killer T (iNKT) cells are self-reactive lymphocytes, yet how this lineage attains

172 y is defective elimination and/or control of self-reactive lymphocytes.

173 f the mechanisms that maintain inactivity of self-reactive lymphocytes.

174 Using a series of polyclonal and transgenic self-reactive models harboring the analogous mutation in

175 demyelinating disease of the CNS mediated by self-reactive, myelin-specific T cells.

176 er the association between the production of self-reactive NAbs and NAbs that afford protection again

177 indings indicate that although production of self-reactive NAbs can be independent of germline D(H) s

178 n vivo calcineurin inhibition leads the most self-reactive naive CD4 T cells to adopt the phenotype o

179 at are optimized for the selection of weakly self-reactive, naive T-cell clones.

180 Self-reactive natural Abs initiate injury following isch

181 ly conserved MPER is a target of potent, non-self-reactive neutralizing antibodies, suggesting that H

182 T cells prevents the harmful accumulation of self-reactive pathogenic T cells in vital organs.

183 is difficult to assess the entire contained self-reactive peripheral T cell repertoire in healthy in

184 ells (Tregs) and enriches this repertoire in self-reactive receptors, contributing to its vast divers

185 ance in autoimmunity is thought to depend on self-reactive regulatory T cells (Tregs).

186 A truncated self-reactive repertoire, devoid of high-avidity T cells

187 CD5(low) T cell pool showed that the overall self-reactive response has not only a diverse polyclonal

188 negative selection of superantigen-specific, self-reactive, single-positive thymocytes, and we show t

189 pment enables the production of B cells with self-reactive, skewed specificity receptors that are pec

190 chain usage and enrichment for low-affinity self-reactive specificities in murine marginal zone and

191 B cell development, promoting enrichment of self-reactive specificities into the follicular mature c

192 However, purging of immature and mature self-reactive T and B cells is incomplete and may also r

193 pply to autoimmune diseases involving clonal self-reactive T and B lymphocytes--a process referred to

194 2D affinity measurements of three of these self-reactive T cell clones demonstrated a normal off-ra

195 formation of immunological synapses (IS) in self-reactive T cell clones from patients with multiple

196 Self-reactive T cell clones that escape negative selecti

197 the T cell repertoire but does not eliminate self-reactive T cell clones.

198 ed that even the naive T cell pool contained self-reactive T cell precursors.

199 Multiple studies highlighted the overtly self-reactive T cell repertoire in the diabetes-prone NO

200 Thus, the self-reactive T cell repertoire is controlled by overlap

201 of the PD-L1:B7-1 interaction in regulating self-reactive T cell responses is not yet clear.

202 Consequently, low amounts of high-affinity self-reactive T cells also escaped the thymus following

203 The self-reactive T cells also maintained a high degree of m

204 importance of Foxp3(+) Tregs in controlling self-reactive T cells and preventing autoimmunity is wel

205 tributing to a reduction in the frequency of self-reactive T cells and resistance to autoimmunity.

206 eloping thymocytes, resulting in deletion of self-reactive T cells and supporting regulatory T cell d

207 Activation of self-reactive T cells and their trafficking to target ti

208 ion of abundant cytokine mRNAs is limited in self-reactive T cells and, thus, identify posttranscript

209 uster of differentiation 1c (CD1c)-dependent self-reactive T cells are abundant in human blood, but s

210 However, if these mechanisms fail, self-reactive T cells are activated and autoimmune respo

211 Although many self-reactive T cells are eliminated by negative selecti

212 However, it remains unknown how peripheral self-reactive T cells are specifically instructed to bec

213 Research into how self-reactive T cells are tolerized in lymph nodes has f

214 ought to be an autoimmune condition in which self-reactive T cells attack insulin-secreting pancreati

215 sclerosis is an autoimmune disease in which self-reactive T cells attack oligodendrocytes that myeli

216 and nonendocrine manifestations initiated by self-reactive T cells because of AIRE mutation-induced d

217 ry thymic epithelial cells (mTECs) eliminate self-reactive T cells by displaying a diverse repertoire

218 It has been shown that self-reactive T cells can be detected in the periphery.

219 Thus, self-reactive T cells can become pathogenic in the targe

220 Self-reactive T cells can escape thymic deletion and the

221 All self-reactive T cells contained a large number of phosph

222 The failure to eliminate self-reactive T cells during negative selection is a pre

223 of autoimmunity requires the elimination of self-reactive T cells during their development in the th

224 TCR repertoire enables Treg cells to control self-reactive T cells effectively, especially when thymi

225 enable acquisition of effector functions by self-reactive T cells encountering large amounts of self

226 facilitate escape from negative selection by self-reactive T cells encountering very small amounts of

227 or negative selection, sufficient numbers of self-reactive T cells escape deletion and create an incr

228 lity to generate effector cytokine proteins, self-reactive T cells express large amounts of cytokine

229 Individual self-reactive T cells have been discovered in both human

230 cells may play an important role in keeping self-reactive T cells in check.

231 rance by dominant suppression of potentially self-reactive T cells in peripheral tissues.

232 When potentially self-reactive T cells in the periphery were activated, t

233 herefore, regulates the early development of self-reactive T cells in the thymus and plays a key role

234 nological tolerance requires the deletion of self-reactive T cells in the thymus.

235 uses expressing OVA-peptide variants induced self-reactive T cells in vivo that matured into memory T

236 ection occurs because potentially pathogenic self-reactive T cells included in the pool of intermedia

237 Activation of self-reactive T cells is a major driver to autoimmunity

238 Because the deletion of self-reactive T cells is incomplete, thymic development

239 affinity in modulating the pathogenicity of self-reactive T cells is less established.

240 Self-reactive T cells must escape thymic negative select

241 xist largely as distinct pathways to repress self-reactive T cells remains incompletely understood.

242 However, the molecular identity of these self-reactive T cells remains largely elusive.

243 Self-reactive T cells that escape elimination in the thy

244 Foxp3 is expressed in a fraction of self-reactive T cells that escape negative selection in

245 s exist to prevent autoimmune destruction by self-reactive T cells that escape thymic deletion.

246 Tregs are critical for control of self-reactive T cells that escape thymic selection and e

247 ncluding multiple sclerosis, are mediated by self-reactive T cells that have escaped the deletional m

248 quiescent tissue-resident dendritic cells to self-reactive T cells that have escaped thymic negative

249 which regulates immune tolerance) that allow self-reactive T cells to enter the periphery.

250 Such compensatory mechanisms can allow self-reactive T cells with altered TCR-binding propertie

251 In T cell-mediated autoimmune diseases, self-reactive T cells with known antigen specificity app

252 Whereas thymic education eliminates most self-reactive T cells, additional mechanisms to promote

253 s between tolerogenic dendritic cells (DCs), self-reactive T cells, and T regulatory cells (Tregs) co

254 Microbial peptides can activate self-reactive T cells, but the structural basis for such

255 ion of apoptosis resulted in more persistent self-reactive T cells, but these cells became anergic to

256 o also cause deletion of larger fractions of self-reactive T cells, leading to a detrimental reductio

257 sing the transcription factor Foxp3 suppress self-reactive T cells, prevent autoimmunity, and help co

258 ntation and epitope-dependent elimination of self-reactive T cells, which may explain why the fat10 g

259 Further, TCRs found on potentially self-reactive T cells, with an activated phenotype (CD4+

260 y dangerous effect of enabling the escape of self-reactive T cells.

261 immune pathways but is primarily mediated by self-reactive T cells.

262 reby allowing us to characterize the exposed self-reactive T cells.

263 he recognition of multiple GAD65 peptides by self-reactive T cells.

264 akdown of tolerance mechanism and priming of self-reactive T cells.

265 immune responses and autoimmunity caused by self-reactive T cells.

266 lity to modulate the activation threshold of self-reactive T cells.

267 hymic expression of self-Ags and deletion of self-reactive T cells.

268 s from the mechanisms that usually eliminate self-reactive T cells.

269 echanism underlying the anergic phenotype of self-reactive T cells.

270 l tolerance by suppressing the activation of self-reactive T cells.

271 of IFNgamma secretion in the preferentially self-reactive T(reg) cell pool does not cause systemic a

272 SG to CD1c enables the binding of human CD1c self-reactive T-cell receptors.

273 that provide a footprint for binding of CD1c self-reactive T-cell receptors.

274 These data show how binding by a self-reactive TCR favors crossreactivity between self an

275 ugh the expression of a newly generated, non-self-reactive TCR.

276 Two broad categories of self-reactive TCRs can be clearly distinguished: (i) TCR

277 an permit the survival of T cells expressing self-reactive TCRs that nonetheless bind with a traditio

278 ing that there are multiple unusual ways for self-reactive TCRs to bind their pMHC ligand.

279 cells pose an autoimmune hazard by allowing self-reactive TCRs to escape thymic selection.

280 x are distinct from previously characterized self-reactive TCRs, indicating that there are multiple u

281 apeutic TCR surface expression and generates self-reactive TCRs.

282 DR3beta robustly promoted the development of self-reactive TCRs.

283 Once induced, the self-reactive TH17 cells promoted auto-inflammation and

284 In the thymus, high-affinity, self-reactive thymocytes are eliminated from the pool of

285 However, many self-reactive thymocytes first encounter ubiquitous self

286 utoimmunity by limiting agonist selection of self-reactive thymocytes into the Treg cell lineage.

287 Negative selection against highly self-reactive thymocytes is critical for preventing auto

288 icity as a primary determinant for selecting self-reactive thymocytes to become Treg cells in a multi

289 rimarily mediated through clonal deletion of self-reactive thymocytes, is critical for establishing s

290 m is not required for the clonal deletion of self-reactive thymocytes, suggesting the existence of no

291 Aire results in impaired clonal deletion of self-reactive thymocytes, which escape into the peripher

292 TSAs), which are presented and help tolerize self-reactive thymocytes.

293 sets the activation threshold of potentially self-reactive TLR7.

294 r B cell tolerance via positive selection of self-reactive transitional B cells.

295 quency of these cells are similar to that of self-reactive Tregs in the absence of cognate infection.

296 which TCR affinity regulates the function of self-reactive Tregs is largely unknown.

297 lusion of cells expressing the intrinsically self-reactive V(H)81X from both pools.

298 Hence, B cells expressing germline-encoded self-reactive VH4-34 antibodies may represent an innate-

299 Our results show that non-self-reactive virus-neutralizing mAbs elicited during SA

300 ecludes secondary rearrangements that delete self-reactive VJ rearranged genes.