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

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

15 gainst PICA between conventional T cells and nTregs.

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

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

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

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

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

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

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

23 Importantly, blood nTreg CD39/CD26 profile remained constant over a 2-y per

24 Based on CD39/CD26 markers, blood nTreg analysis revealed the presence of five different c

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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 Natural regulatory T cells (nTregs) ensure the control of self-tolerance and are cur

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

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

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

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

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

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

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

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

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

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

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

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

63 3(+) naturally occurring regulatory T cells (nTregs).

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

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

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

67 e and microenvironmental cytokines condition nTreg activities, which include blockade of autoreactive

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

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

70 on, was associated with a transient decrease nTreg.

71 ts that developed food allergy had decreased nTreg at birth, and the labour-associated decrease in nT

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 skin allografts through indirectly expanded nTreg leading to dominant tolerance without additional i

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

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

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

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

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

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

89 cific suppressive capacity of these expanded nTregs was tested.

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

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

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

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

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

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

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

97 l differences in activation requirements for nTregs versus iTregs.

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

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

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

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

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

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

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

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

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

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

108 not induce Th2 and Th17 differentiation from nTreg cells.

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

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

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

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

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

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

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

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

117 and male sex was each associated with higher nTreg in infancy.

118 way plays in suppressive activities of human nTreg.

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

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

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

122 birth, and the labour-associated decrease in nTreg at birth was more evident among infants with subse

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

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

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

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

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

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

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

130 could facilitate optimal mature moDC-induced nTreg expansion.

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

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

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

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

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

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

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

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

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

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

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

142 the suppressive activities of iTreg but not nTreg.

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

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

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

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

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

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

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

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

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

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

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

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

155 ific mechanisms to control the generation of nTreg cells.

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

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 The proportion of nTreg at birth is a major determinant of the proportion

160 A higher proportion of nTreg at birth, larger birth size and male sex was each

161 a birth cohort (n = 1074), the proportion of nTreg in the CD4(+) T-cell compartment was measured by f

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

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

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

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

166 enotypical and functional characteristics of nTregs.

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

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 Regarding nTreg functional plasticity, both maturation stage and m

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

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

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

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

205 actors (gestation, labour, sex, birth size), nTreg at each time point and food allergy at 1 year were

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

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

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

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

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

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

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

213 to generate functional alloantigen-specific nTregs.

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

215 uppressed on coculture with antigen-specific nTregs.

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

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

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

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

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 food allergy, and there was no evidence that nTreg at either 6 or 12 months were related to food alle

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

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

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

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

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

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

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

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

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

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

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

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

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

247 leukemia illustrate the potential use of the nTreg CD39/CD26 profile as a blood biomarker to monitor

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

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

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

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

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

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

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

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

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

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

258 and prevent GVHD in an equivalent fashion to nTregs.

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

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

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

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

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

264 of indirectly activated natural Foxp3 Treg (nTreg) and depletion of Foxp3 Treg abrogates skin-graft

265 nship between perinatal factors, naive Treg (nTreg) over the first postnatal year and development of

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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