ライフサイエンスコーパス: IL-15

1 IL-15 activates STAT5 proteins, which can form dimers or

2 IL-15 and its receptor alpha (IL-15Ralpha) are co-expres

3 IL-15 augmented mammalian target of rapamycin (mTOR) sig

4 IL-15 bound to the IL-15Ralpha-chain (IL-15Ralpha) is pr

5 IL-15 equally sustains wild-type and Il7ra(-/-) ILC surv

6 IL-15 further induces the expression of chemokine recept

7 IL-15 has been implicated as a key regulator of T and NK

8 IL-15 is an essential cytokine known to promote T cell s

9 IL-15 KO mice showed improved survival, attenuated hypot

10 IL-15 may be an effective therapeutic target for the att

11 IL-15 primes NK cells for effector functions, which were

12 IL-15 regulates central and effector memory CD8 T cell (

13 IL-15 SA caused NK cell activation as indicated by incre

14 IL-15 SA treatment also exacerbated septic shock caused

15 IL-15 SA treatment amplified endotoxin shock, which was

16 IL-15 superagonist treatment potently inhibited acute HI

17 IL-15-activated CD40L(+) ILC3s helped B-cell survival, p

18 ut dependent on IL-18 in synergy with IL-12, IL-15 and/or interferon-alpha/beta.

19 We report that upon activation with IL-12, IL-15, and IL-18 human NK cells express NKG2D ligands of

20 pecific activation with the cytokines IL-12, IL-15, and IL-18 or in response to antigens or cytomegal

21 cell activation, augmented levels of IL-12, IL-15, IL-18, IFN-gamma, and TNF were detected in patien

22 l cytokines, including IFN-gamma1, IL-4/13A, IL-15, IL-17D, IL-10, and TGF-beta1, perhaps indicating

23 Increased expression of interleukin 15 (IL-15) in leukemic blasts is associated with increased r

24 normoxia and in response to interleukin 15 (IL-15) priming using a 2 x 2 factorial design.

25 limiting the availability of interleukin 15 (IL-15), and administration of IL-15/IL-15Ralpha or immun

26 The production of interleukin 15 (IL-15), IL-18, gamma interferon (IFN-gamma), granulocyte

27 ly, UV-HSV-1 synergizes with interleukin-15 (IL-15) and IL-2 in inducing activation and cytolytic act

28 Interleukin-15 (IL-15) is essential for the development and maintenance

29 activation of NK cells using interleukin-15 (IL-15) plus 4-1BBL upregulates activating receptor expre

30 CH1 and RBPJ, as well as the interleukin-15 (IL-15) receptor complex, the latter enhancing IL-15 auto

31 a interferon (IFN-alpha) and interleukin-15 (IL-15), this study explored the therapeutic potential of

32 phocytes and increased serum interleukin-15 (IL-15).

33 nd was mimicked by exogenous interleukin-15 (IL-15).

34 homeostatic pathway defined by IL-15/IL-15R (IL-15 receptor) interaction and the inflammasome pathway

35 provides evidence that the sushi-IL-15Ralpha/IL-15 fusion protein RLI enhances antitumor activity of

36 In contrast to IL-2, IL-15 mediated stronger signaling through the IL-2/15 re

37 age increases in Th1 cytokines such as IL-2, IL-15, and granulocyte-macrophage colony-stimulating fac

38 noclonal antibodies in the presence of IL-2, IL-15, and IL-1beta.

39 and phosphospecific antibodies, a novel IL-2/IL-15 inducible IL-2Rbeta phosphorylation site (Thr-450)

40 These expressed the common IL-2/IL-15 receptors and another subset of APOBEC3G anti-vira

41 -9, IL-10, fibroblast growth factor 2, IL-7, IL-15, and transforming growth factor alpha) but lower l

42 ssociated with diminished interleukin (IL)-7/IL-15-dependent homeostatic proliferation resulting in i

43 d significant up-regulation of AMCFII, IL-8, IL-15, VEGFA, LIF, FASL, CXCL11, CCL4, CCL25 and down-re

44 n (IL) receptors for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21.

45 Consistently, mTOR inhibition abrogated IL-15-induced cell function advantages.

46 e NK cells that allows these cells to access IL-15-rich microenvironments.

47 -treated DC with mononuclear cells activates IL-15 and IL-1beta receptors on CD4(+) T cells, elicitin

48 Neutralisation of the high-affinity IL-15 receptor binding subunit, IL-15ralpha in elderly m

49 mbinant cytokines (rIL-15, rTNFalpha) and an IL-15 receptor neutralising antibody.

50 at the high-affinity interactions between an IL-15 superagonist (IL-15N72D) and the extracellular IL-

51 es, as memory CD8 T cells proliferated in an IL-15-dependent manner.

52 ALT-803 is an IL-15 superagonist complex that has been developed as a

53 cluding the possibility that retention of an IL-15 transpresenting support system is key to extending

54 CD4-1(+) T cells and the establishment of an IL-15-dependent CD4-1(+) T cell line.

55 innate immune response, by treatment with an IL-15 superagonist increases their anti-HIV activity and

56 The role of IL-12 and IL-15 in the enhancement of natural killer cell activity

57 timulation with cytokines (IL-12, IL-18, and IL-15).

58 Interleukin 2 and IL-15 are two closely related cytokines, displaying impo

59 ibe a previously unexpected role to IL-2 and IL-15 as instigators of CD8(+) T-cell exhaustion during

60 , one variant, H9-RETR, antagonized IL-2 and IL-15 better than blocking antibodies against IL-2Ralpha

61 We demonstrate that IL-2 and IL-15 treatment significantly induce CD300c expression e

62 y blocked proliferation elicited by IL-2 and IL-15, but only an inhibitor targeting the PI3K/Akt/mTOR

63 IL-2 and IL-15, members of the gamma chain (gammac) family of cyt

64 We demonstrate a direct impact of IL-2 and IL-15, two common gamma-chain-dependent cytokines, on CD

65 ared the ability of interleukin-2 (IL-2) and IL-15 to sustain human NK-cell functions following cytok

66 investigated the interplay between IL-32 and IL-15 and their role in NK cell activity.

67 CI 1.3-6.1]), IL-12p40 (1.8 [1.0-3.4]), and IL-15 (2.0 [1.1-3.7]), versus controls.

68 D3/28-activated T cells expanded in IL-7 and IL-15 produced greater expansion of memory stem T cells

69 in (gammac) receptor but that, like IL-7 and IL-15, induced expression of the lineage-specifying tran

70 ion was heritably preserved during IL-7- and IL-15-mediated in vitro cell proliferation.

71 intrahepatic lymphocytes from IFN-alpha- and IL-15-treated animals were transferred to new HBV carrie

72 tion is a physiologic feature of asthma, and IL-15 might have an important role in asthma pathogenesi

73 ded in vitro in the presence of TGF-beta and IL-15, IL-9 was the most abundant among 16 analyzed cyto

74 ntiation of tumor-infiltrating NK cells, and IL-15 deficiency, but not Nfil3 deficiency, results in a

75 ere assessed in Il15 gene-deficient mice and IL-15-overexpressing mice in an allergen-induced murine

76 e and accumulate in the spleen where TCR and IL-15/STAT5 signaling promotes their conversion to CD8al

77 C57BL/6 wild-type (WT) and IL-15(-/-) mice were sensitized and challenged with oval

78 arly complete and maintained as long as anti-IL-15 treatment was given, TEM depletion was countered b

79 t of IL-15 inhibition with a rhesusized anti-IL-15 mAb on T and NK cell dynamics in rhesus macaques.

80 Strikingly, anti-IL-15 treatment resulted in rapid depletion of NK cells

81 aintained very high turnover throughout anti-IL-15 treatment.

82 K cell depletion through treatment with anti-IL-15 monoclonal antibody during chronic SIVagm infectio

83 As IL-15 transpresentation occurs in the context of cell-to

84 f malignant Lin(-)IEL lines as powerfully as IL-15.

85 ly isolated NK cells with cytokines, such as IL-15, IL-12, or IL-18, does not activate LFA-1 but incr

86 nhibitory ligands and from cytokines such as IL-15.

87 s demonstrate a novel mechanism to attenuate IL-15-dependent NK cell proliferation and suggest that i

88 Because IL-15 is fundamental to T-cell memory, we incorporated i

89 Because IL-15 promotes NK cell activation, we investigated the i

90 anscriptional analysis revealed that besides IL-15, IL-32 was the only other cytokine expressed by hu

91 Su et al demonstrate associations between IL 15 serum levels and the outcome of patients with Stev

92 ng compounds, 36 of which were found to bind IL-15, to inhibit the binding of IL-15 to the IL-2Rbeta

93 Blocking IL-15 signals also significantly impacts tissue-specific

94 etween CD4(+)CD44(+) memory T cells and both IL-15 of the homeostatic and IL-1beta of the inflammasom

95 s I-related chain A and B and membrane-bound IL-15 in IFN-DC-mediated NK cell activation and early IF

96 uated the restoration of mortality caused by IL-15 SA.

97 nation of the homeostatic pathway defined by IL-15/IL-15R (IL-15 receptor) interaction and the inflam

98 TOR pathway blocked proliferation induced by IL-15 as well as the CD4(+) T-cell cytokines.

99 ion of the NKG2A(+) cell line NKL induced by IL-15 transpresentation was inhibited by HLA-E.

100 icantly delayed tumor progression induced by IL-15:IL-15Ralpha-coated nanoparticles in comparison wit

101 t gene expression differences were primed by IL-15 and only manifested after cytokine withdrawal.

102 Aspergillus species extract-challenged CC10-IL-15 bitransgenic mice exhibited significantly reduced

103 d compared with non-doxycycline-exposed CC10-IL-15 bitransgenic mice.

104 ther validated in doxycycline-inducible CC10-IL-15 bitransgenic mice.

105 proliferation of NK, NK-T, and CD8+ T cells, IL-15 plays important roles in innate and adaptative imm

106 given immediately prior to septic challenge, IL-15-neutralizing IgG M96 failed to protect against sep

107 xpressing CAR with a membrane-bound chimeric IL-15 (mbIL15).

108 Consequently, IL-15 availability hypothetically defines the carrying c

109 c strategies, the immunostimulatory cytokine IL-15 could represent a serious candidate for the reacti

110 ese lymphocytes is dependent on the cytokine IL-15, but not the transcription factor Nfil3 that is re

111 -1-related alarmins, as well as the cytokine IL-15, which is important for T cell and NK cell homeost

112 d synergy between two stimulating cytokines, IL-15 and IFN-alpha, which, given together, constitute a

113 s of sepsis was assessed in IL-15-deficient (IL-15 knockout, KO) mice.

114 (-)IELs is driven by epithelial cell-derived IL-15.

115 treatment with high-dose, but not low-dose, IL-15 eliminated the metabolic requirement for receptor

116 -32alpha also acted on DCs by downregulating IL-15-induced IL-18 production, an important cytokine in

117 Moreover, elevated IL-15 expression in the lymph nodes of untreated HIV-1-i

118 infected patients and suggests that elevated IL-15 may also drive CD8+ T cell expansion that is linke

119 ata demonstrate that mice with an endogenous IL-15 deficiency are susceptible to the development of s

120 In conclusion, endogenous IL-15 does not directly augment the pathogenesis of seps

121 L-15) receptor complex, the latter enhancing IL-15 autocrine signaling.

122 Exogenous IL-15 exacerbates the severity of sepsis by activating N

123 However, exogenous IL-15 may have a limited impact on patients with cancer

124 hat cooperates with an ILC3 survival factor, IL-15, to induce proliferation of human ILC3s, as well a

125 describe a novel oncogenic pathway featuring IL-15, miR-29b, and BRD4 in CTCL and suggest targeting o

126 Finally, IL-15 robustly stimulated the PI3K/Akt/mTOR and MEK/ERK

127 iguration-dependent" mechanism of action for IL-15:IL-15Ralpha (heterodimeric IL-15 or hetIL-15) wher

128 VHD, donor T cells compete with NK cells for IL-15 thereby inducing profound defects in NK-cell recon

129 d pathogens as the result of competition for IL-15.

130 ation via IL-15Ralpha and its importance for IL-15 function have been described, the full effect of t

131 These follicles were strongly positive for IL-15, which was primarily presented in its membrane-bou

132 ticles displayed higher levels of functional IL-15 on the cell surface, implicating a mechanism for n

133 pe 1 (TH1)-related markers interferon-gamma, IL-15, and granulocyte-macrophage colony-stimulating fac

134 action for IL-15:IL-15Ralpha (heterodimeric IL-15 or hetIL-15) where the manner by which IL-15:IL-15

135 study provides mechanistic insight into how IL-15 controls the generation of memory CD8 T cells and

136 Additionally, we found that a human IL-15 agonist (ALT-803) improved airway resistance and c

137 RLI consists of human IL-15 covalently linked to the human IL-15Ralpha sushi(+

138 maximum-tolerated dose of recombinant human IL-15 (rhIL-15) administered as a daily intravenous bolu

139 T-PCR confirmed positive synergistic hypoxia/IL-15 interactions for genes of key regulatory and metab

140 ditional analytes (IP-10, IL-12/23p40, IFNy, IL-15) were found to be elevated in HIV/HCV coinfection

141 scovering small-molecule inhibitors impeding IL-15/IL-15R interaction.

142 are dispensable for the induction of AAD in IL-15-deficient mice.

143 , the pathogenesis of sepsis was assessed in IL-15-deficient (IL-15 knockout, KO) mice.

144 uppressed the enhancement of eosinophilia in IL-15(-/-) animals to levels observed in WT mice, but ha

145 ficient in IL-15Ralpha signaling, but not in IL-15 itself.

146 vivo, and transcriptional analysis of TEM in IL-15-inhibited monkeys revealed engagement of the JAK/S

147 ence of microenvironmental signals including IL-15, and were capable of polarizing both blood and col

148 led between ILC3s and B cells: ILC3s induced IL-15 production in B cells through B cell-activating fa

149 ogether, these data reveal that inflammatory IL-15 promotes optimal responses by memory CD8+ T cells.

150 that IL-32alpha acts on NK cells to inhibit IL-15-mediated STAT5 phosphorylation and to suppress the

151 BiG efficiently inhibited IL-15- and IL-2-dependent functions of primary cells, in

152 ledge by providing mechanistic insights into IL-15 SA-mediated immunotoxicity.

153 Mice lacking IL-15 have selective defects in populations of several p

154 After stimulation with the gammac-ligand IL-15, gammac-deficient keratinocytes show significantly

155 Like IL-15, these cytokines were found to increase the phosph

156 ty of the IL-15 superagonist receptor-linker-IL-15 (RLI), designed to bypass the need of endogenous I

157 IFN-gamma, IL-2, IL-6, and IL-1beta) or low (IL-15, TNF-alpha, IL-12 p70, IL-17A, GM-CSF, IL-12 p40,

158 that activated human NK cells were mediating IL-15 superagonist-induced inhibition of acute HIV-1 inf

159 The CD8(+) T cell mitogen IL-15, which was increased in oxazolone-challenged skin

160 pproach, leading to the first small-molecule IL-15 inhibitor with sub-micromolar activity.

161 nanoparticles in comparison with monovalent IL-15:IL-15Ralpha.

162 Localization of multivalent IL-15:IL-15Ralpha and encapsulated antigen to the same D

163 A robust response to ODN+IL-15 was positively linked to presence of chromosomal a

164 In the absence of IL-15, OVA-challenged mice exhibited enhanced bronchial

165 cell populations collapse in the absence of IL-15, TEM can be maintained in the face of IL-15 inhibi

166 ay support TEM homeostasis in the absence of IL-15.

167 nterleukin 15 (IL-15), and administration of IL-15/IL-15Ralpha or immune suppression with rapamycin c

168 und to bind IL-15, to inhibit the binding of IL-15 to the IL-2Rbeta chain or the proliferation of IL-

169 The combination of IL-15 with soluble IL-15Ralpha generates a complex terme

170 s confirmed that autocrine concentrations of IL-15 also support myogenesis.

171 ationale for its key functions downstream of IL-15.

172 -presenting cells to highlight the effect of IL-15 configuration on DCs, we showed that artificial an

173 s this question by determining the effect of IL-15 inhibition with a rhesusized anti-IL-15 mAb on T a

174 In this study, the effect of IL-15 SA on physiologic and immunologic functions of mic

175 However, the effect of IL-15 signaling on CD4(+) T cell activity is incompletel

176 The effects of IL-15 on human skeletal muscle growth and development re

177 Finally, expression of IL-15 correlated with cytolytic immune functions in pati

178 housed in EE, in mediating the expression of IL-15 in CD11b(+) cells.

179 ALL cells, we demonstrate that expression of IL-15 in leukemic cells is associated with the activatio

180 e found that type I IFN-driven expression of IL-15 in response to viral infection prepares memory CD8

181 Hair follicle expression of IL-15 was required for CD8(+) TRM cells, and IL-7 for CD

182 both constitutive and induced expression of IL-15, as well as IL-15Ralpha mRNA expression in murine

183 IL-15, TEM can be maintained in the face of IL-15 inhibition by the activity of other homeostatic re

184 The impact of IL-15 superagonist-induced activation of human NK cells

185 ll functions and argue for implementation of IL-15 in adoptive NK-cell cancer therapy.

186 ur findings suggest a feedback inhibition of IL-15-mediated NK cell activity by IL-32alpha.

187 hat increased peripheral and local levels of IL-15 amplify the pathogenic potential of CD4(+)CD28(-)

188 Moreover, the association of high levels of IL-15 expression with inflammatory and autoimmune diseas

189 Although the cellular mechanism of IL-15 trans-presentation via IL-15Ralpha and its importa

190 The novel mechanism of IL-15 transfer to the surface of antigen-processing DCs

191 8(+) T cells and re-established mortality of IL-15 KO mice during septic shock.

192 The superior performance of IL-15-stimulated NK cells was also observed using a clin

193 sing DCs may explain the enhanced potency of IL-15:IL-15Ralpha-coated nanoparticles for antigen deliv

194 In the presence of IL-15 inhibition, TEM became increasingly more sensitive

195 both IFN-beta-dependent cis-presentation of IL-15 on NK cells and engagement of the 2B4-CD48 pathway

196 Importantly, while trans-presentation of IL-15 results in STAT5 activation and maintenance of the

197 gulation of NKp44, and trans-presentation of IL-15.

198 the IL-2Rbeta chain or the proliferation of IL-15-dependent cells or both.

199 We tested the hypothesis that regulation of IL-15 is critical for preservation of allergen-induced a

200 by Cish) as a critical negative regulator of IL-15 signaling in NK cells.

201 studies showed that the systemic toxicity of IL-15 SA was mediated by hyperproliferation of activated

202 Adoptive transfer of IL-15 activated CXCR3(+) innate CD8(+) T cells conferred

203 hanism for nanoparticle-mediated transfer of IL-15 to the DC surface.

204 Therefore, transpresentation of IL-15 is subject to downregulation by MHC class I-specif

205 senting cells, allowing transpresentation of IL-15 to immune cells bearing IL-2RbetagammaC and stimul

206 those reported in recent clinical trials of IL-15 in patients with refractory cancers and advance cu

207 n but not for survival, or did not depend on IL-15 for either process.

208 ed distinct TRM populations that depended on IL-15 for homeostatic proliferation and survival, depend

209 atic proliferation and survival, depended on IL-15 for homeostatic proliferation but not for survival

210 killing, a function we show is dependent on IL-15.

211 ced H4K12ac, enhancing the effect of EtOH on IL-15, RANTES, TGF-beta1, and TNF-alpha cytokines while

212 ficient secretion of IL-18, but not IL-12 or IL-15 and/or induction of NK cell apoptosis.

213 noclonal antibodies targeting either IL-2 or IL-15 receptors and safer than inhibitors of downstream

214 proliferation after stimulation with IL-2 or IL-15, suggesting that STAT5 signaling is affected.

215 the in vivo relevance of this pathway in our IL-15 transgenic mouse model of CTCL by showing that int

216 (gammac)-dependent cytokines, in particular IL-15.

217 for self-antigen interacting with peripheral IL-15.

218 ound that the same conditions (TGF-beta plus IL-15) strongly enhanced the expression of additional ge

219 TH1 cells are responsive to trans-presented IL-15.

220 tificial antigen-presenting cells presenting IL-15:IL-15Ralpha increased the sensitivity and magnitud

221 We found that trans-presenting IL-15:IL-15Ralpha in a multivalent fashion on the surfac

222 ion and maintenance of the TH1 gene program, IL-15 treatment alone allows for increased Bcl-6 express

223 ulation of human NK cells with a recombinant IL-15 superagonist significantly induced their expressio

224 that boosted circulating TEM do not require IL-15 for maintenance.

225 iNKT cell development requires IL-15, and we found that sgammac interfered with IL-15 s

226 Treatment with IL-15 superagonist (IL-15 SA, IL-15/IL-15Ralpha complex) regenerated NK and mCD8(+) T

227 d with our observation that myotubes secrete IL-15 in response to TNFalpha stimulation supports the n

228 Sequential IL-15 or antigen exposure followed by TGFbeta induces li

229 High serum IL-15 levels were associated with high peak blood CAR(+)

230 n of advanced-stage lymphoma, and high serum IL-15 levels were associated with the effectiveness of t

231 onses occurs despite deficiencies in several IL-15-dependent cell types including NK, NKT, and gammad

232 reduce the proliferation induced by soluble IL-15.

233 In contrast, soluble IL-15 (sIL-15) complexes are upregulated only after TBI

234 hepatocytes as the major producer of soluble IL-15/IL-15Ralpha complexes in the liver.

235 nerates a complex termed IL-15 superagonist (IL-15 SA) that possesses greater biological activity tha

236 Treatment with IL-15 superagonist (IL-15 SA, IL-15/IL-15Ralpha complex) regenerated NK and

237 We report that cell surface IL-15 expression is upregulated during lymphopenia induc

238 terestingly, the cellular profile of surface IL-15 expression is distinct in each model.

239 caffold for creating multispecific, targeted IL-15-based immunotherapeutic agents and may serve as a

240 of various antagonistic approaches targeting IL-15.

241 luble IL-15Ralpha generates a complex termed IL-15 superagonist (IL-15 SA) that possesses greater bio

242 t possesses greater biological activity than IL-15 alone.

243 In this study, we demonstrate that IL-15 influences the generation of memory CD8 T cells by

244 ng immunohistochemistry, we demonstrate that IL-15 is mainly produced by astrocytes and infiltrating

245 Lastly, we provide evidence that IL-15 induced by inflammatory signals in response to lym

246 We report our novel finding that IL-15 has a potent inhibitory effect on the airway obstr

247 In this study, we found that IL-15 is a potent inducer of IL-32alpha in DCs.

248 We hypothesized that IL-15 promotes the pathogenesis of sepsis by maintaining

249 We therefore hypothesized that IL-15(-/-) mice will have reduced inflammatory responses

250 NFalpha stimulation supports the notion that IL-15 serves to mitigate inflammatory skeletal muscle lo

251 We made a novel observation that IL-15 deficiency promotes baseline airway resistance in

252 Mechanistically, we observed that IL-15-mediated protection of airway obstruction is assoc

253 Here, we report that IL-15(-/-) mice developed enhanced allergic responses in

254 in vitro transmigration studies reveal that IL-15 selectively attracts CD4(+)CD28(-) T cells of MS p

255 ally, flow cytometric analyses revealed that IL-15 increases the proliferation and production of GM-C

256 Last, we show that IL-15 complexes delivered locally to mucosal tissues wit

257 clonal proliferation/survival, we show that IL-15 precludes TLR-9-induced apoptosis and permits sign

258 Together, these results suggest that IL-15 drives bystander activation of CD8+ T cells, which

259 cell lines and in mouse models suggest that IL-15 promotes myogenesis and may protect against the in

260 identified a point mutation in exon 7 of the IL-15 gene in Pedigree 191 (deficient memory (DM)) of N-

261 rk, we studied the antitumor activity of the IL-15 superagonist receptor-linker-IL-15 (RLI), designed

262 have been described, the full effect of the IL-15:IL-15Ralpha configuration on responding cells is n

263 ory B cells in vivo seem to utilize only the IL-15/IL-15R homeostatic pathway, although the prolifera

264 Interestingly, Bim does not restrict the IL-15-driven maturation of CD8alphaalpha cells that is c

265 ferred is through trans-presentation via the IL-15 receptor alpha subunit.

266 ht NK cells from MM patients primed with the IL-15 receptor agonist ALT-803 in vivo displayed enhance

267 observed in humanized mice treated with the IL-15 superagonist, demonstrating that activated human N

268 STAT5 phosphorylation and to suppress their IL-15-induced effector molecule expression and cytolytic

269 hodepletion, the mechanisms regulating these IL-15 responses are unclear.

270 dependent, but can persist partially through IL-15 signalling.

271 Thus, IL-15 plays a major role in peripheral maintenance of NK

272 nt failure to differentiate appropriately to IL-15.

273 Effector mechanisms contributing to IL-15-based priming included improved cytotoxic protein

274 rs and subsequently undergo apoptosis due to IL-15 starvation.

275 Moreover, exposure to IL-15 allowed more rapid division of memory CD8+ T cells

276 of Cish rendered NK cells hypersensitive to IL-15, as evidenced by enhanced proliferation, survival,

277 t5 DKI NK cells have normal proliferation to IL-15 but are susceptible to death upon cytokine withdra

278 lower production of IFN-gamma in response to IL-15 and reduced proliferation after stimulation with I

279 Cish was rapidly induced in response to IL-15, and deletion of Cish rendered NK cells hypersensi

280 de repeats 1 (IFIT1) promoter in response to IL-15, whereas STAT5 phosphorylation and DNA binding to

281 imary NK cells in response to transpresented IL-15 was reduced by engagement of either KIR2DL1 or KIR

282 erentially expanded in spleen and liver upon IL-15 SA treatment.

283 Using IL-15 as a growth factor, we have selected a lymphoid ce

284 Whereas IL-15 has well-established roles in stimulating lymphocy

285 h B cell-activating factor receptor, whereas IL-15, a potent growth factor for ILC3s, induced CD40 li

286 To determine whether IL-15(-/-) mice have attenuated allergic responses in a

287 One mechanism by which IL-15 activity is conferred is through trans-presentatio

288 IL-15 or hetIL-15) where the manner by which IL-15:IL-15Ralpha molecules are presented to target cell

289 e studies demonstrate that the form in which IL-15 is expressed, its kinetics and cellular sources, a

290 t of peripheral blood mononuclear cells with IL-15 induced a cycling, granzyme B+ phenotype in CD8+ T

291 as an adjuvant, alone or in combination with IL-15, for allogeneic donor mononuclear cell infusions t

292 tronger effector function in comparison with IL-15.

293 Strikingly, DCs incubated with IL-15:IL-15Ralpha-coated nanoparticles displayed higher

294 5, and we found that sgammac interfered with IL-15 signaling to suppress iNKT cell generation in the

295 synergistic activity with RLI, but not with IL-15.

296 igm by demonstrating that brief priming with IL-15 markedly enhanced the antitumor response of CD56br

297 increase in CD4(+) T cells was recorded with IL-15 receptors, APOBEC3G and CC chemokines, the latter

298 Importantly, inhibition studies with IL-15 antibodies and IL-1betaR inhibitor suggest that bo

299 TGF-beta, together with IL-15, induces a regulatory phenotype in Vdelta2 T cells

300 Treatment with IL-15 superagonist (IL-15 SA, IL-15/IL-15Ralpha complex)