ライフサイエンスコーパス: nTreg

1 nTreg cell development is instructed by the T cell recep

2 nTreg cells (CD4(+)CD25(+)) were isolated from WT mice a

3 nTregs from CD8(-/-) mice failed to suppress lung allerg

4 nTregs from IL-6(-/-) mice were suppressive, but lost th

5 nTregs, however, are sparse and lack alloantigen specifi

6 Because activated nTreg cells are known to induce granzyme B-mediated B-ce

7 In this study, we demonstrate that activated nTreg and activated conventional T cells differ in their

8 This allows nTregs to be more sensitive to activation and more cross

9 In this paper, we demonstrated an nTreg-specific mechanism controlling their Th2 conversio

10 anistic links between MHC, autoimmunity, and nTreg diversity identified in this study are discussed.

11 Such Foxp3-transduced CD4 T cells and nTreg cells expressed T-bet, GATA-3, or retinoic acid-re

12 ofiles, the Foxp3-transduced CD4 T cells and nTreg cells remained immune suppressive.

13 fferences and similarities between iTreg and nTreg cells is yet to be defined.

14 ata confirm that allergen-specific iTreg and nTreg have active roles in asthma tolerance and that iTr

15 The suppressive function of both iTreg and nTreg, however, is not affected by the loss of PD-1H.

16 gainst PICA between conventional T cells and nTregs.

17 loss, mice were treated with both iTregs and nTregs where one marked subset was selectively IL-10 def

18 al suppressive function between NO-Tregs and nTregs and indicate specialization of the regulatory mec

19 state, IL-10-producing aTreg/Tr1 as well as nTreg and effector Th17 CD4(+) cells are expanded in viv

20 T-bet(-/-) nTreg displayed instability in the graft, failing to sup

21 T-bet(-/-) nTreg had no functional deficiency in vitro but failed t

22 distribution in tissues, so that T-bet(-/-) nTreg remained in the grafts rather than migrating to ly

23 In an islet allograft model, T-bet(-/-) nTreg, but not induced Treg, failed to prolong graft sur

24 m expectation, however, the function of both nTreg and iTreg was independent on robust NFAT levels, r

25 the direct suppression of B-cell function by nTreg cells or to impaired regulation of T-helper functi

26 ral proliferation due to viral production by nTreg itself and not to reduced Natural Killer (NK) cell

27 decreased IL-6R expression and signaling by nTregs.

28 The isolated CD154(+) nTregs could be most efficiently expanded by specific an

29 fostering the generation of Foxp3(-)CD25(+) nTreg cell precursors at the CD69(+)CCR7(+)CCR9(-) stage

30 nt through the generation of Foxp3(-)CD25(+) nTreg cell precursors.

31 ve capacity of adoptively transferred CD4(+) nTregs by increasing the stability of Foxp3 expression.

32 Importantly, isolated 4-1BB(+)CD40L(-) nTreg maintain the nTreg phenotype and alloantigen-react

33 Alloantigen-reactive 4-1BB(+)CD40L(-) nTreg were characterized by a completely demethylated Tr

34 ype recipients prior to transfer of CD8(-/-) nTregs restored suppression.

35 ing Foxp3(+)CD4(+)CD25(+) T regulatory cell (nTreg)-mediated suppression of lung allergic responses i

36 ted and expanded natural T regulatory cells (nTreg).

37 tion of Foxp3(+) natural regulatory T cells (nTreg cells) and the continued maturation of positively

38 natural CD25(+)Foxp3(+) regulatory T cells (nTreg) and induced CD25(+)Foxp3(+) regulatory T cells (i

39 Naturally occurring regulatory T cells (nTreg) are crucial for maintaining tolerance to self and

40 ived naturally occurring regulatory T cells (nTreg) depend on calcium signals, the Foxp3 gene harbors

41 Natural regulatory T cells (nTreg) play a central role in the induction and maintena

42 is essential for natural regulatory T cells (nTreg) to regulate Th1 inflammation, but whether T-bet c

43 us, analogous to natural regulatory T cells (nTreg).

44 , in the form of natural regulatory T-cells (nTreg), that globally dampen the inflammatory response.

45 5(+) naturally occurring T regulatory cells (nTregs) in wild-type (WT) hosts.

46 ng CD4(+)CD25(+)Foxp3(+) T regulatory cells (nTregs) regulate lung allergic responses through product

47 R repertoires of natural regulatory T cells (nTregs) and conventional CD4(+) T cells (Tconv) capable

48 ance mediated by natural regulatory T cells (nTregs) and development of autoimmune ovarian dysgenesis

49 -derived Foxp3+CD25+CD4+ regulatory T cells (nTregs) are pivotal for the maintenance of self-toleranc

50 ng CD4(+)CD25(+)FoxP3(+) regulatory T cells (nTregs) have an essential role in maintenance of immune

51 of natural CD4(+)CD25(+) regulatory T cells (nTregs) in controlling graft rejection and the mechanism

52 he low number of natural regulatory T cells (nTregs) in the circulation specific for a particular Ag

53 ion of naturally derived regulatory T cells (nTregs) in the thymus through lymphocyte-specific protei

54 Although CD4(+)CD25(+) regulatory T cells (nTregs) induce tolerance that inhibits insulitis and T1D

55 ific naturally occurring regulatory T cells (nTregs) is required to obtain sufficient numbers of cell

56 occurring CD4(+)Foxp3(+) regulatory T cells (nTregs) may account for their inability to control chron

57 gate the role of natural regulatory T cells (nTregs) on the mitigation of GvHD by AzaC, instead focus

58 Natural regulatory T cells (nTregs) play an important role in tolerance; however, th

59 ved Foxp3(+) natural regulatory CD4 T cells (nTregs) prevent autoimmunity through control of pathogen

60 Natural regulatory T cells (nTregs) that develop in the thymus are essential to limi

61 "Natural" regulatory T cells (nTregs) that express the transcription factor Foxp3 and

62 age of naturally arising regulatory T cells (nTregs) that is segregated from effector CD4(+) T cells

63 tution of CD4(+) natural regulatory T cells (nTregs), CD4(+) induced Tregs (iTregs), and CD8(+) iTreg

64 , or selected as natural regulatory T cells (nTregs).

65 3(+) naturally occurring regulatory T cells (nTregs).

66 and regulatory (natural T regulatory cells [nTregs] and adaptive Treg cells [aTreg/type 1 regulatory

67 Indeed, compared with naive CD4 T cells, nTreg expressed elevated levels of GATA-3 independent of

68 Under the polarizing conditions, nTreg cells failed to differentiate into Th2 and Th17 ce

69 In contrast, nTregs from JNK1(-/-) mice, similar to WT nTregs, were f

70 Intriguingly, IL-4 production by converted nTreg cells is required for Th2 differentiation of coexi

71 d-induced TNFR-related protein are converted nTregs into IL-13-producing CD4(+) T cells mediating lun

72 ced apoptosis of TGF-beta receptor-deficient nTreg cells was associated with high expression of proap

73 required for both spleen- and thymus-derived nTreg-mediated suppression, but is not required for iTre

74 pool was comprised equally of donor-derived nTregs and iTregs.

75 aling, which may preferentially disadvantage nTreg selection.

76 neic BMT, induce PD-1 ligand-dependent donor nTreg proliferation, and maintain potent graft-versus-ho

77 cipient, rather than the donor, drives donor nTreg proliferation.

78 Following STAT6(-/-) BMT, donor nTregs demonstrated no loss of proliferation in vivo, in

79 t mice suggested that both preexisting donor nTregs and the generation of iTregs in the recipient mic

80 t-derived Gr-1(low)CD11c(+) cells with donor nTregs.

81 A highly enriched nTreg fraction (CD4(+)CD25(bright)CD127(-) T cells) was

82 neration sequencing of mRNA of moDC-expanded nTregs revealed a strong induction of Treg-associated mR

83 Allogeneic mature moDC-expanded nTregs were at low ratios (<1:320), potent suppressors o

84 The allogeneic mature moDC-expanded nTregs were fully characterized by analysis of the demet

85 Mature moDC-expanded nTregs were highly demethylated at the Treg-specific dem

86 e bystander suppressive capacity of expanded nTregs presents a major clinical challenge for nTreg-bas

87 A minority of the expanded nTregs produced IL-10, IL-2, IFN-gamma, and TNF-alpha, b

88 cific suppressive capacity of these expanded nTregs was tested.

89 ndicating an intrinsic mechanism that favors nTreg-to-Th2 differentiation.

90 n contrast to FCRL3(-) nTreg cells, FCRL3(+) nTreg cells were not stimulated to proliferate by the ad

91 However, in contrast to FCRL3(-) nTreg cells, FCRL3(+) nTreg cells were not stimulated to

92 regs presents a major clinical challenge for nTreg-based therapeutic treatment of autoimmune diseases

93 ted region in the FOXP3 gene as a marker for nTreg and FOXP3 messenger RNA expression as a marker for

94 And GATA-3 was required for nTreg-to-Th2 conversion.

95 rate that TGF-beta signaling is required for nTregs to survive PICA.

96 l differences in activation requirements for nTregs versus iTregs.

97 aging-guided longitudinal analyses, we found nTreg depletion did not affect systemic trafficking and

98 cells induced potent H-2K(b+)CD4(+)Foxp3(+) nTreg proliferation in vitro in 72-h MLRs.

99 In contrast, Foxp3(+) nTreg cell development is medullary dependent, with mTEC

100 TLI/ATS + BMT restored day-6 donor Foxp3(+) nTreg proliferation and protection from CD8 effector T c

101 C compartment is a prerequisite for Foxp3(+) nTreg cell development through the generation of Foxp3(-

102 ine/chemokine production, Helios(-) FOXP3(+) nTreg clones were demethylated at the FOXP3 Treg-specifi

103 ression, human alloantigen-reactive Foxp3(+) nTreg can be directly isolated from MLR cultures with hi

104 Like naturally arising Foxp3(+) nTregs, the converted Tregs are anergic cells with decre

105 cing and using in vitro Ag-specific Foxp3(+) nTregs to control graft rejection in transplantation.

106 However, ISL-DCs from nTreg-deficient recipient mice showed increased in vitro

107 not induce Th2 and Th17 differentiation from nTreg cells.

108 CDR3 sequences from nTregs displayed a divergent pattern of Jalpha usage, mi

109 Furthermore, nTregs in the model are enriched with MHC-specific TCRs.

110 e CCL3 and IFN-gamma compared with Helios(+) nTregs.

111 larizing conditions, Helios(+) and Helios(-) nTreg clones had an equal ability to produce IFN-gamma.

112 We found that both Helios(+) and Helios(-) nTreg clones have a similar suppressive capacity, as wel

113 Helios(-) nTregs, however, produced significantly more CCL3 and IF

114 r the coexistence of Helios(+) and Helios(-) nTregs in human peripheral blood.

115 AD patients showed significantly higher nTreg-cell counts compared to STAT3-HIES and control ind

116 ts suggest that the FCRL3(+) subset of human nTreg cells identified in this study arise in vivo and F

117 way plays in suppressive activities of human nTreg.

118 Thus, human nTreg characterized by the presence of CD39 and the low

119 nscription factor, may specifically identify nTregs, allowing specific tracking of Tregs from differe

120 lete reversal of all GITR-induced changes in nTreg phenotype and function, with full restoration of s

121 the thymic niche is not a limiting factor in nTreg development.

122 n of T-bet and interferon-gamma induction in nTreg cells.

123 AT levels, reflected by less nuclear NFAT in nTreg and iTreg.

124 may account for this GATA-3 upregulation in nTreg cells, because ectopic expression of Foxp3 prefere

125 CD8 in regulating the production of IL-6 in nTregs was demonstrated by the loss of suppression and i

126 hypotheses of TCR-dependent and -independent nTreg development.

127 poised to differentiate better into induced nTreg cells, both in vitro and in vivo, representing a n

128 could facilitate optimal mature moDC-induced nTreg expansion.

129 d skin-derived DCs were superior in inducing nTreg expansion compared with immature moDCs or PBMCs in

130 and migration-related molecules, influencing nTreg distribution in tissues, so that T-bet(-/-) nTreg

131 matory response to virus as well as inherent nTreg-mediated regulation of Th1 recruitment and activat

132 In vitro, targeting TIM-3 did not inhibit nTreg-mediated suppression of Th1 alloreactive cells but

133 ta signaling, arginase 1, or iNOS, inhibited nTreg proliferation in cocultures of recipient-derived G

134 Our data indicate that intragraft nTreg are unable to restrain alloreactivity leading to r

135 cant driver of viral proliferation; and (iv) nTreg-mediated DC deactivation plays a significant role

136 t the observed difference in frequency of LN nTregs is controlled by Ada1/H2.

137 Through yet-to-be-defined mechanisms, nTreg cells were recently shown to convert into proinfla

138 activation of Foxp3 gene expression in mouse nTregs, and consequently the loss of suppressor phenotyp

139 lyzed genome-wide methylation in human naive nTreg (rTreg) and conventional naive CD4(+) T cells (Nai

140 arently normal thymic development of the NOD nTreg lineage, TCR diversity within the selected reperto

141 the suppressive activities of iTreg but not nTreg.

142 s significantly upregulated in Teffs but not nTregs after treatment with AzaC.

143 let transplantation model, alloTregs but not nTregs prolonged survival of islet allografts without an

144 gulatory (nTreg) cells, we developed a novel nTreg model on pure nonobese diabetic background using e

145 We compared the abilities of nTreg and iTreg, both from OVA-TCR-transgenic OTII mice,

146 ghlight further complexity in the control of nTreg repertoire diversity.

147 of Foxp3 expression led to Th2 conversion of nTreg cells in vivo.

148 s in vivo, suggesting that Th2 conversion of nTreg cells might be critical for directing Th2 immune r

149 Th2 conversion of nTreg cells was not due to their inability to become Th1

150 model we sought to address the net effect of nTreg activation and its specific functions as well as i

151 for iTreg development, because frequency of nTreg remained unaltered in mice lacking NFAT1, NFAT2, o

152 Although the frequency of nTreg was increased in Fil(+), IL-10 was overwhelmingly

153 We examined the functions of nTreg and iTreg cells by adoptive transfer immunotherapy

154 ific mechanisms to control the generation of nTreg cells.

155 To explore the methylation landscape of nTreg, we analyzed genome-wide methylation in human naiv

156 These data suggest a modified model of nTreg development in which TCR-CBM-dependent signals are

157 The relative high percentage of nTreg after rejection was not related to the number of r

158 IL2, IFNgamma, and IL17A, the percentage of nTreg was significantly higher in EMB with histological

159 Whereas the transcriptional signatures of nTreg and in vivo-derived iTreg cells were closely match

160 nting a novel peripheral precursor subset of nTreg cells to which we refer to as pre-nTreg cells.

161 Transfer of nTreg cells enhanced lung allergic responses, as did tra

162 cells, preceded T1D onset in the absence of nTregs, and suggested a novel in vivo function of nTregs

163 -) animals, we have assessed the activity of nTregs in the absence of IL-10 both under in vitro and i

164 enotypical and functional characteristics of nTregs.

165 The IL-10(-/-) animals depleted of nTregs before ocular infection showed more severe SK les

166 quantitative differences in the frequency of nTregs in the lymph nodes (LNs), but not spleen or thymu

167 Thus, the regulatory function of nTregs can be subverted by reducing the expression of Fo

168 s, and suggested a novel in vivo function of nTregs in T1D prevention by regulating local invasivenes

169 lone did not restore suppressive function of nTregs, preactivation in the presence of TGF-beta did.

170 on and abrogates the suppressive function of nTregs.

171 ustaining the stability and functionality of nTregs in the presence of IL-6.

172 K, was detected in the immunoprecipitates of nTregs from wild-type but not JNK- or GITR-deficient mic

173 st time to our knowledge, the involvement of nTregs in the two pathways of allorecognition in a murin

174 s in regulating the suppressive phenotype of nTregs through control of IL-6 production.

175 olled mechanism regulating the prevalence of nTregs in autoimmune disease susceptibility.

176 Thus, GITR stimulation of nTregs and signaling through JNK2, but not JNK1, trigger

177 In vitro stimulation of nTregs with GITR ligand increased phosphorylation of c-J

178 Of interest, adoptive transfer of nTregs even from arthritic mice treated with atRA suppre

179 Transfer of nTregs from CD8(-/-) donors reconstituted with CD8(+) T

180 and increases in IL-6 following transfer of nTregs from wild-type donors depleted of CD8(+) cells.

181 genetically targeted nTregs was dependent on nTreg to effector T-cell ratios and in vivo nTreg activa

182 As monotherapy, only nTreg cells prevented disease lethality, but did not sup

183 mmunization, mice were treated with iTreg or nTreg cells that were generated or expanded in vitro.

184 Inhibition of JNK in WT nTregs or nTregs from GITR(-/-)and JNK2(-/-) mice failed to enhanc

185 the T-cell receptor (TCR) beta-chain of our nTreg model was not only sufficient to bias T-cell devel

186 In the latter pathway, nTregs used at a physiological ratio failed to delay gra

187 chain transgenic mice to generate polyclonal nTreg and Tconv populations specific for a foreign Ag.

188 t of nTreg cells to which we refer to as pre-nTreg cells.

189 amma, and TNF-alpha, but few IL-17-producing nTregs were found.

190 Instead, TGF-beta promotes nTreg cell survival by antagonizing T cell negative sele

191 h factor-beta (TGF-beta) signaling protected nTreg cells and antigen-stimulated conventional T cells

192 Delivery of 5 x 10(5) purified nTreg reduced allergen challenge-induced airway IL-4 (p

193 10) in vitro or in vivo, whereas we purified nTreg from allergen-naive mice and exposed them to DC10

194 possible to identify functional Ag-reactive nTregs cells for a range of different common viral and v

195 The Ag-reactive nTregs could be recognized with great specificity by ind

196 tion and expansion of functional Ag-reactive nTregs is possible and of potential benefit for specific

197 These CD154(+) Ag-reactive nTregs showed a memory phenotype and shared all phenotyp

198 The frequency of these Ag-reactive nTregs within the nTreg population is strikingly similar

199 Although anti-IL-13 reduced nTreg cell-mediated enhancement, it was ineffective in i

200 Thus, T-bet regulates nTreg migration into afferent lymphatics and dLN and con

201 function of "natural-arising" T regulatory (nTreg) cells, we developed a novel nTreg model on pure n

202 hrough the T cell receptor during selection: nTreg cells, iNKT cells, nIELs, and nTh17s.

203 Unexpectedly, our results showed nTreg depletion led to accelerated invasive insulitis do

204 Sorted nTreg cells with the surface phenotype FCRL3(+) and FCRL

205 stablish cellular therapies with Ag-specific nTreg aiming at a specific inhibition of unwanted immuni

206 bility to simultaneously analyze Ag-specific nTreg and conventional T cells, and to establish cellula

207 However, Ag-specific nTreg are present at extremely low frequencies in the pe

208 onally distinct and that foreign Ag-specific nTreg populations are constrained by a limited TCR reper

209 reactions, only the transfer of Ag-specific nTreg represents the appropriate therapeutic option.

210 These data indicate that foreign Ag-specific nTregs and Tconv are clonally distinct and that foreign

211 for expansion of stable alloantigen-specific nTregs with superior suppressive function.

212 to generate functional alloantigen-specific nTregs.

213 nterestingly, cotransfer of antigen-specific nTregs suppresses the up-regulation of Foxp3 by inhibiti

214 uppressed on coculture with antigen-specific nTregs.

215 rease in GrB-mediated apoptosis in Spi6(-/-) nTregs and impaired suppression of alloreactive T cells

216 e transfer experiments showed that Spi6(-/-) nTregs were less effective than wild type nTregs in supp

217 redundant regulatory subset that supplements nTreg cells, in part by expanding TCR diversity within r

218 hough both natural and induced regulatory T (nTreg and iTreg) cells can enforce tolerance, the mechan

219 man naturally occurring CD4(+) regulatory T (nTreg) cells (CD4(+)CD25(+)CD127(low)).

220 with both naturally occurring regulatory T (nTreg) cells and inducible regulatory T (iTreg) cells ex

221 us-derived naturally occurring regulatory T (nTreg) cells are necessary for immunological self-tolera

222 Naturally occurring regulatory T (nTreg) cells express Foxp3 and were originally discovere

223 cytokine expression in natural regulatory T (nTreg) cells is unclear.

224 lso favor expansion of natural regulatory T (nTreg) cells.

225 f iTreg cells, but not natural regulatory T (nTreg) cells.

226 Intravenous infusion of CD19-targeted nTregs into SCID-Beige mice with systemic Raji tumors tr

227 Optimal suppression by genetically targeted nTregs was dependent on nTreg to effector T-cell ratios

228 ls through the eradication of tumor-targeted nTregs.

229 Relative to Tconv, nTreg expansion was delayed, although a higher proportio

230 eg cells are more stable and functional than nTreg cells in mice with established autoimmunity.

231 gnaling may be greater for iTreg rather than nTreg cells during GvHD.

232 and recent clinical trials demonstrate that nTreg can control alloreactivity.

233 How T cell deletion is regulated so that nTreg cells are generated is unclear.

234 Our results suggest that nTreg cell commitment is independent of TGF-beta signali

235 C to optimally protect against GvHD and that nTregs, unlike Teffs (CD3(+)FOXP3(-)), are resistant to

236 These results demonstrate that nTregs are essential for AzaC to fully protect against G

237 Finally, by demonstrating that nTregs require TNF-alpha for optimal function whereas iT

238 We found that nTregs treated with atRA were resistant to Th17 and othe

239 We show that nTregs used at a physiological ratio were able to delay

240 We suggest that nTregs treated with atRA may represent a novel treatment

241 are consistent with reports suggesting that nTregs are activated in sites of inflammation while iTre

242 Spectratype analysis revealed that both the nTreg and Tconv responses were different and characteriz

243 In conclusion, the nTreg population mirrors the effector T cell population

244 DC10 engaged the nTreg in a cognate fashion in Forster (or fluorescence)

245 isolated 4-1BB(+)CD40L(-) nTreg maintain the nTreg phenotype and alloantigen-reactivity after in vitr

246 Deletion of STAT3 within only the nTreg cell population was not sufficient to protect agai

247 sential to commit immature thymocytes to the nTreg lineage.

248 uency of these Ag-reactive nTregs within the nTreg population is strikingly similar to the frequency

249 ive Helios(+) and Helios(-) Tregs within the nTreg population, we isolated single-cell clones from ea

250 Therefore, nTreg fate revision is not restricted to the Treg-Th17 a

251 resonance energy transfer assays, and these nTreg reduced in vitro OVA-asthmatic Th2 effector T cell

252 n of cyclophosphamide in the setting of this nTreg-mediated hostile microenvironment was able to rest

253 induction of the regulatory response through nTreg activation expedites viral proliferation due to vi

254 Abnormal TNFR2(-/-) nTreg function was not associated with an in vivo decrea

255 overcome the functional defect in TNFR2(-/-) nTregs.

256 iTreg cells, similar to nTreg cells, exhibit functional plasticity and can be co

257 and prevent GVHD in an equivalent fashion to nTregs.

258 egs (139-iTregs) have a phenotype similar to nTregs, but additionally express an intermediate level o

259 me TCR as this somatic cell nuclear transfer nTreg model had a reduced capability to differentiate in

260 Following transfer, nTreg cells exhibited decreased FoxP3 and Bcl-2 expressi

261 nt of lung allergic responses by transferred nTreg and iTreg cells differed.

262 eased expression of IL-13 in the transferred nTregs.

263 ptive transfer model in which TCR-transgenic nTregs were or were not depleted before transplantation.

264 Prototypic natural Treg (nTreg) can be reliably identified by demethylation at th

265 y two pathways: instability of natural Treg (nTreg) cells and inhibition of induced Treg (iTreg) cell

266 tional CD4(+) T cells, whereas natural Treg (nTreg) cells are selected by high-avidity interactions i

267 ls demonstrate advantages over natural Treg (nTreg) cells in terms of increased number of starting po

268 valent expanded thymus-derived natural Treg (nTreg) cells on established collagen-induced arthritis (

269 ve, Th1, Th2, Th17, iTreg, and natural Treg (nTreg) cells.

270 creased whereas the genesis of natural Treg (nTreg) remains normal.

271 or TNFR2-expression on murine natural Tregs (nTregs) and induced Tregs (iTregs) in mediating suppress

272 ental cues for thymic-derived natural Tregs (nTregs) and periphery-generated adaptive Tregs (aTregs).

273 e that both induced Tregs and natural Tregs (nTregs) increase their intracellular expression of GrB a

274 the expansion of preexisting natural Tregs (nTregs) or from de novo generation of inducible Tregs (i

275 by increased proliferation of natural Tregs (nTregs) within the single positive CD4 thymocyte compart

276 In contrast, natural Tregs (nTregs), which suppressed Th1 cells, failed to suppress

277 ion Foxp3 gene are considered natural Tregs (nTregs).

278 distinct subsets: naturally occurring Tregs (nTregs) that develop in the thymus, and induced Tregs (i

279 We found that wild-type nTreg cells expressing reduced levels of Foxp3 but not t

280 -) nTregs were less effective than wild type nTregs in suppressing graft-versus-host disease because

281 However, unlike nTregs, both iTreg populations lost Foxp3 expression wit

282 ayed, although a higher proportion of viable nTregs had divided after 72 h.

283 In vitro nTregs modified to express CD19-targeted CARs efficientl

284 nTreg to effector T-cell ratios and in vivo nTreg activation.

285 When nTregs were present but IL-10 deficient, iTreg-produced

286 he indirect alloreactivity pathway only when nTregs were used in high numbers.

287 nd to decrease chronic inflammation, whereas nTreg cells prevent autoimmunity and raise the activatio

288 obilized anti-CD3 and anti-CD28 Abs, whereas nTregs expand robustly under the same conditions, sugges

289 rphan receptor gammat but not T-bet, whereas nTregs suppressed T-bet but not retinoic acid-related or

290 16:1 responder to suppressor ratio, whereas nTregs suppressed at 4:1.

291 It remains elusive whether nTregs can convert into effector cells by turning off th

292 anti-TNF-alpha therapy may relate to whether nTregs or iTregs have the predominant regulatory role in

293 f Foxp3-sufficient conventional T cells with nTreg cells reconstituted the iTreg pool and established

294 contrasting, when possible, iTreg cells with nTreg cells.

295 igen-induced Tregs (alloTregs) compared with nTregs.

296 We found that preactivated WKO nTreg cells failed to effectively suppress B-cell prolif

297 evaluate the regulatory capabilities of WKO nTregs on B lymphocytes.

298 Inhibition of JNK in WT nTregs or nTregs from GITR(-/-)and JNK2(-/-) mice failed

299 t, nTregs from JNK1(-/-) mice, similar to WT nTregs, were fully effective in enhancing responses.

300 ) mice were restimulated in culture to yield nTregs (EGFP(+)) and Tconv (EGFP(-)) defined by their an