ライフサイエンスコーパス: cell expansion

1 ion of multiple self-antigens that promote B cell expansion.

2 increased IL-1beta and dermal gammadeltaT17 cell expansion.

3 in IL-9 expression results in decreased mast cell expansion.

4 tructed mDCs, which mediated subsequent Th17 cell expansion.

5 h, smaller cotyledons, and arrested pavement cell expansion.

6 of Gbeta proteins in controlling anisotropic cell expansion.

7 of proinflammatory monocyte and T regulatory cell expansion.

8 ctivity for the establishment of human CD34+ cell expansion.

9 icrotubule arrays that determine the axis of cell expansion.

10 s into how membrane-bound IL-21 regulates NK cell expansion.

11 aling with downstream metabolic burst and NK cell expansion.

12 t a map of cell state changes during naive T-cell expansion.

13 ell persistence (P = .05) but not peak CAR T-cell expansion.

14 shape and are unstable at the time scales of cell expansion.

15 ting this molecule as a trigger for CD4(+) T cell expansion.

16 was the most effective in reducing leukemic cell expansion.

17 ctively drive and specify the extent of stem-cell expansion.

18 an in vivo model of squamous cancer-stromal cell expansion.

19 division and cell merging that are shaped by cell expansion.

20 ementary processes: biomass biosynthesis and cell expansion.

21 , but also plays a direct role in regulating cell expansion.

22 at this MPK cascade affects auxin-influenced cell expansion.

23 PRMT5 is an important modulator of CD4(+) T cell expansion.

24 microtubule organization during anisotropic cell expansion.

25 o the emerging description of auxin-mediated cell expansion.

26 d by a combination of cell proliferation and cell expansion.

27 ility of these regulatory ILCs to suppress T cell expansion.

28 y of biomass, while its extensibility limits cell expansion.

29 1/2-dependent manner, facilitating GZMB(+) B cell expansion.

30 ream of MPK1 in influencing auxin-responsive cell expansion.

31 beta-cell FoxM1 pathway and suppresses beta-cell expansion.

32 d that RHM1 is required to promote epidermal cell expansion.

33 mone that inhibits root growth by repressing cell expansion.

34 ngation growth of shoot tissues by promoting cell expansion.

35 at may provide a dynamic module for altering cell expansion.

36 great impact on cell wall properties during cell expansion.

37 activation, heightened IL-2 production and T cell expansion.

38 cal manner to mediate rapid and controlled T-cell expansion.

39 ed chain of events necessary for efficient T cell expansion.

40 kewed T cell receptor repertoire and broad T cell expansion.

41 g and development in plants and is vital for cell expansion.

42 cytokines, despite equivalent in vivo CAR T-cell expansion.

43 a subset of auxin inducible genes related to cell expansion.

44 elaxation in the cell wall, which constrains cell expansion.

45 ponses with RBD-specific CD8(+) and CD4(+) T cell expansion.

46 tode parasitism-related immune responses and cell expansion.

47 imultaneously acting to limit auxin-mediated cell expansion.

48 undescribed role for TCPs in the control of cell expansion.

49 rtual memory cells without clonal effector T cell expansion.

50 al importance for neonatal and adaptive beta-cell expansion.

51 t effect of water potential on turgor-driven cell expansion.

52 o periods of organ growth, cell division and cell expansion.

53 t a dual role for LGO on endoreplication and cell expansion.

54 of NOTCH1 activity suppresses cancer/stromal cells expansion.

55 (MSCs) using a dynamic culture technique for cells expansion.

56 s are confounded by poor levels of erythroid cell expansion, aberrant or incomplete erythroid differe

57 proliferated and reached an average 40-fold cell expansion after 2 weeks, compared with 6-fold expan

58 e propionate promoted Sema4a-dependent T reg cell expansion, ameliorating both diseases.

59 ters (GCs) are the primary sites of clonal B cell expansion and affinity maturation, directing the pr

60 Precise coordination of cell expansion and cell proliferation underlies growth i

61 ults from the coordination of two processes: cell expansion and cell-cycle arrest.

62 s were treated with amitrole, which inhibits cell expansion and chloroplast function.

63 de novo methylation programs that restrict T cell expansion and clonal diversity during PD-1 blockade

64 s with the delivery of exocytic vesicles for cell expansion and counterbalancing endocytic uptake.

65 Repertoire analysis revealed broad clonal T cell expansion and curtailed interferon response in seve

66 functions and pathways during hematopoietic cell expansion and development.

67 T cell expansion and differentiation are critically depend

68 AZ signaling mechanism that coordinates stem cell expansion and differentiation during organ renewal.

69 ificant contribution from cardiac progenitor cell expansion and differentiation in culture.

70 treated endothelial cells impaired satellite cell expansion and differentiation via decreased prolife

71 s methylome, which is robustly propagated on cell expansion and differentiation.

72 ulatory genes causing changes in anisotropic cell expansion and division patterns [3-5].

73 role over STAT5B in promoting gammadeltaT17 cell expansion and downregulating gut-associated T-bet.

74 lated strongly with large antibody-secreting cell expansion and early production of high concentratio

75 In vivo, Yap is indispensable for Sca-1(+) cell expansion and early tumour initiation and displays

76 ific ablation of Sptlc2 impaired antiviral-T-cell expansion and effector function.

77 patients with SLE of both races displayed T-cell expansion and elevated expression of type I and II

78 ng antigen-loaded dendritic cells improved T cell expansion and favored central memory T cell differe

79 d TCM is an intriguing strategy to enhance T cell expansion and function against pathogens or tumors.

80 on site, we determined that optimal CD8(+) T cell expansion and function were induced by the peptides

81 tic pH regulation, steering the rate of root cell expansion and gravitropic response.

82 sed pH abrogates wall loosening required for cell expansion and growth.

83 receptor agonist that induces oligoclonal T-cell expansion and has single-agent activity in advanced

84 The actin cytoskeleton is required for cell expansion and implicated in cellular responses to t

85 r-GDF9 can effectively promote mouse cumulus cell expansion and improve oocyte quality in vitro repre

86 acilitates several-fold greater polyclonal T-cell expansion and improved antigen-specific enrichment

87 ammation specifically characterized by CD8 T-cell expansion and improved by IFNg blockade.

88 y promoted growth of ENS cell spheres during cell expansion and increased the number of newborn neuro

89 , a surface protein that drives polyclonal B cell expansion and induces cell death in the absence of

90 results indicate that PGX2 both functions in cell expansion and influences secondary wall formation,

91 s immune responses by restraining effector T cell expansion and limiting nonspecific damage to the ho

92 urvival and proliferation, and promoted stem cell expansion and lymph node metastasis.

93 with omeprazole as was allergen-induced mast cell expansion and mast cell activation in the intestine

94 e presence of IL-12-induced optimal CD8(+) T cell expansion and melanoma regression; however, adverse

95 ic deletion of Adrb2 resulted in impaired NK cell expansion and memory during MCMV challenge, in part

96 ression, by mitigating conventional CD4(+) T-cell expansion and modulating their inflammatory program

97 estinal inflammation, tissue damage, donor T cell expansion and mortality in allo-HSCT.

98 f Gli proteins with GANT61 inhibited Gli1(+) cell expansion and myofibroblast differentiation and att

99 Despite overt T-cell expansion and neutrophilia, a reduction in conventi

100 of CASP8 on the magnitude of antiviral CD8 T cell expansion and not on contraction.

101 itively selected GC B cells and reduced GC B cell expansion and PC formation.

102 ng on the endogenous IL-7 to enhance donor T cell expansion and persistence after lymphodepleting che

103 Across clinical trials, T cell expansion and persistence following adoptive cell t

104 omeostasis and is a prerequisite for plastic cell expansion and plant growth.

105 ) differentially affects peripheral CD8(+) T-cell expansion and possibly thymic selection.

106 ulatory programs, which constrain effector T cell expansion and prevent increasing oligoclonality but

107 that BRD4 is required for hematopoietic stem cell expansion and progenitor development.

108 e as a paracrine signal that sustains tumour cell expansion and progression, suggesting that apelin i

109 trol distinct biological mechanisms, such as cell expansion and proliferation, will enhance crop yiel

110 rea evolution involves parallel processes of cell expansion and proliferation.

111 lar assemblies are shown to be permissive to cell expansion and remodeling, making this hydrogel syst

112 The AM forms through limited cell expansion and requires the recruitment of numerous

113 cogenic lesions that facilitate unrestrained cell expansion and resistance to antiproliferative signa

114 alized auxin increase balances wound-induced cell expansion and restorative division rates in a dose-

115 ramming of stem cells and prevented Sca-1(+) cell expansion and sporadic tumour initiation in mutant

116 is essential for suppressing epidermal stem cell expansion and the emergence of an abnormal stem cel

117 hanisms of auxin-mediated rapid promotion of cell expansion and underlying rearrangement of cell wall

118 n = 5) were associated with attenuated CAR T cell expansion and/or rapid attrition of functional CAR

119 in the cumulus cells, much increased cumulus cell expansion, and an accelerated severance of cytoplas

120 nuria, glomerular filtration rate, mesangial cell expansion, and collagen type IV and transforming gr

121 PL activation enhances antitumor function, T-cell expansion, and cytokine production and preserves a

122 ting to normal B cell responses, malignant B cell expansion, and generic principles relating to recep

123 ell wall loosening functions associated with cell expansion, and grew larger than wild-type anthers d

124 sed IL-5 production, group 2 innate lymphoid cell expansion, and host resistance to the hookworm para

125 to increased cell proliferation, rather than cell expansion, and increased expression of CYCLIN D3;1-

126 in treatment during secondary CD8 effector T cell expansion, and is dependent on the signaling adapto

127 HA synthesis, promotes FoxP3(+) regulatory T-cell expansion, and prevents autoimmune diabetes.

128 g in epithelial cells, increase Lgr5(+) stem cell expansion, and promote intestinal organoid growth.

129 ges in adaptive immunity, including memory T-cell expansion, and rising prevalence of diabetes in the

130 ng IRF3 also developed lung disease, myeloid cell expansion, and T cell cytopenia.

131 prehensive explanation of how auxin controls cell expansion, and where more research is warranted.

132 studies of human samples, including clonal B-cell expansions, and also for following antibody affinit

133 nd both CD4(+) T-cell cytopenia and CD8(+) T-cell expansion are associated with morbidity and mortali

134 bility that RBK1 effects on auxin-responsive cell expansion are mediated through phosphorylation-depe

135 auxin signaling, cytoskeletal remodeling and cell expansion are poorly understood.

136 It is shown that strong NKG2C(+) NK cell expansions are dominated by single KIR clones, wher

137 N UP RNA19 (SAUR19) subfamily, which promote cell expansion, are repressed by SOB3 and light, and are

138 nic contributions to the osmotica that drive cell expansion, as well as the synthesis of protein, cel

139 display hypersensitivity in auxin-responsive cell expansion assays, suggesting that this MPK cascade

140 isplays hypersensitivity in auxin-responsive cell expansion assays.

141 course of infection, also showed no T or NK cell expansion at the time.

142 ed a strong, synergy, suppressing growth and cell expansion beyond the phenotypic sum of the two sing

143 vo, but resulted in altered systemic myeloid cell expansion, both in the primary tumors and at the di

144 gen-presenting cells for intragraft memory T cell expansion but not to alloantibody production and th

145 nd leaf size by increasing ploidy levels and cell expansion but that cell division can substitute for

146 cepted to be determined by cell division and cell expansion, but, unlike that in animals, the contrib

147 K562-derived aAPC cell line could sustain NK cell expansion by 3 x 10(5)-fold, whereas low expression

148 H(+)-ATPases (PM H(+)-ATPases) to facilitate cell expansion by both loosening the cell wall through a

149 hat iron contributes to activation-induced T cell expansion by positively regulating IL-2R signaling

150 nterleukin-25, which indirectly induces tuft cell expansion by promoting interleukin-13 production by

151 rowth, we found that cellulose synthesis and cell expansion can be uncoupled and are regulated by dif

152 sures of circulating tumor DNA (ctDNA) and T-cell expansion can be used to assess responses to immune

153 circulating tumor DNA dynamic changes and T-cell expansion can be used to guide immune targeted ther

154 he first steps in ripening and that delaying cell expansion can delay ripening providing a possible m

155 IL-1beta and IL-18 and concurrent late CAR T cell expansion characterized the HLH-like syndromes occu

156 These reserves support cell expansion, chloroplast development and root growth

157 le HAM/TSP patients showed a higher clonal T-cell expansion compared to MS and HC, increase of the TC

158 ients at last follow-up, with enhanced CAR T cell expansion compared with published data.

159 to sixty cell passages (P60) under in vitro cell expansion conditions.

160 c.d2 or pp2c.d5 derivatives conferred severe cell expansion defects and corresponding constitutively

161 GH43 loss-of-function mutants exhibited root cell expansion defects in sugar-containing growth media.

162 Biomarker analysis suggested CAR T-cell expansion, despite the absence of systemic disease,

163 Apoplastic H(2) O(2) influences cell expansion, development and defence by its involveme

164 -generation sequencing were used to assess T cell expansion, differentiation, and clonal diversity.

165 c qualities of effective anti-tumor T cells: cell expansion, differentiation, oxidative stress, and g

166 pendent IL-9 production is required for mast cell expansion during allergic intestinal inflammation.

167 dual T1D subjects, consistent with in vivo T cell expansion during disease progression.

168 ls can regulate epithelial KIT(+) progenitor cell expansion during murine salivary gland organogenesi

169 tance of balancing stromal versus adipogenic cell expansion during white adipose tissue development,

170 t is affected in both cell proliferation and cell expansion early during leaf development.

171 xpress second-generation CARs and found that cell expansion enhanced the response to stimulation.

172 These data reveal that the spatiotemporal cell expansion events driving this transition are not de

173 remodeling and a window of tumor-resident T cell expansion following radiation that may be leveraged

174 APCs) are used to mediate scalable ex vivo T-cell expansion for adoptive cell therapy.

175 s supported by spatiotemporal control of the cell expansion gene EXPANSIN 2 (EXPA2).

176 e associated with differential expression of cell-expansion genes.

177 cognized, most publications on age-related T-cell expansions have focused on dominant target proteins

178 y European Americans may protect them from T-cell expansion, heightened activation of interferon path

179 Microtubules influence cell expansion; however, the mechanisms by which environ

180 , MEK1/2 inhibitor treatment up-regulated B1 cell expansion, IgM production, phagocytic receptor expr

181 grasses is driven by cell proliferation and cell expansion in a basal growth zone [3].

182 rived IL-1beta and IL-6 during homeostatic T cell expansion in a clinically relevant model of lymphoa

183 the potential impact of GRAs to drive alpha-cell expansion in adult patients is unclear.

184 t gammadelta TCR expression and gammadelta T cell expansion in AIM.

185 (IFN-I) receptor leads to CXCR5(+) CD8(+) T cell expansion in an IL-27- and STAT1-dependent manner.

186 mediated intestinal stem cell and progenitor cell expansion in CD patients, human cells, and preclini

187 ic skin transplant and alloantigen-induced T cell expansion in draining lymph node experiments.

188 s: T cell-independent Ag induced increased B cell expansion in germinal centers from Duox1(-/-) mice

189 CAR T cell expansion in lymphoid tissue was demonstrated, and

190 raptor deletion ameliorates the aberrant TFH cell expansion in mice lacking Def6.

191 death-independent role of CASP8 during CD8 T cell expansion in mice lacking the confounding impact of

192 FGF2 induces leukemia stem cell expansion in MLL1-rearranged AML.

193 specific IgE production, and intestinal mast cell expansion in offspring.

194 Consistently, beta-cell expansion in response to a high-fat, high-sucrose (

195 ery and stability to adjust plant growth and cell expansion in response to changing environmental con

196 ting cell wall-loosening enzymes that enable cell expansion in shoots.

197 EC-specific ablation of Gja1 restores beta-cell expansion in the aged pancreas.

198 ote cell production in the root meristem and cell expansion in the elongation zone.

199 esii S-morph plants, GLO2 promotes growth by cell expansion in the fused tube of petals and stamen fi

200 lls, but in contrast promotes autoreactive B cell expansion in the germinal center and serum autoanti

201 ree mice with bacteriophages leads to immune cell expansion in the gut.

202 but it did at a cellular level with reduced cell expansion in the hypocotyl relative to the wild typ

203 Further, angiogenesis and beta-cell expansion in the pancreas are coupled by a distinct

204 of RNAi transformants indicated reduction of cell expansion in vascular bundles, particularly on thei

205 e functional in driving Ag-specific CD8(+) T cell expansion in vitro but that this process was defect

206 ollaborates with FLT3-ITD to promote myeloid cell expansion in vivo and that this involves a multitar

207 CAR-T cell expansion in vivo was cell dose dependent.

208 B cells promoted BAFF-independent Treg cell expansion in vivo, as evidenced by the correlation

209 the enzyme Phgdh was essential for CD8(+) T cell expansion in vivo.

210 oach is often limited by the extent of CAR-T cell expansion in vivo.

211 required for metabolic stress-mediated beta-cell expansion in young mice, but with aging, Myc upregu

212 as extracellular vesicle release and myeloid cell expansion, in the establishment of pre-metastatic n

213 iome, thereby inducing inflammation and stem cell expansion, independent of obesity.

214 licing and reverts haematopoietic progenitor cell expansion induced by mutant U2AF1 expression.

215 Gibberellic acid (GA)-mediated cell expansion initiates the seed-to-seedling transition

216 hat in Arabidopsis thaliana seeds, endosperm cell expansion is a key component of germination.

217 Cell expansion is a significant contributor to organ gro

218 Cell expansion is an essential process in plant morphoge

219 per (TFH) cells, is critical as aberrant TFH cell expansion is associated with autoimmune diseases, s

220 and shape of the budding yeast nucleus when cell expansion is inhibited by down-regulating component

221 hip arises naturally from a model in which T cell expansion is limited by decaying levels of presente

222 largely been elucidated, how auxin controls cell expansion is only now attaining molecular-level def

223 This mechanism ensures that cell expansion is properly coordinated with cell divisio

224 We demonstrate that cell expansion is regulated by protein-mediated changes

225 The effect on tendon cell expansion is specific to the geranylgeranylation br

226 (SPR1) protein, which regulates directional cell expansion, is an autonomous +TIP.

227 tical role in germination by enabling embryo cell expansion leading to radicle protrusion, as well as

228 peripheral markers affected by peripheral T-cell expansion, making it difficult to assess the role o

229 y controlling the culture environment during cell expansion may improve the efficacy of stem cell-bas

230 ntigen-specific TCM, resulting in enhanced T cell expansion measured during subsequent booster inject

231 tes that multiple genetic and spatiotemporal cell expansion mechanisms underlie the seed to seedling

232 e lack of impact of Klhl6 deficiency on GC B cell expansion, mutants could contribute to the oncogeni

233 G responses by enhancing early Ag-specific B cell expansion, not by altering B cell development.

234 hese results indicate that although in vitro cell expansion of embryonic tooth mesenchymal cells rend

235 lability of large numbers of cells, in vitro cell expansion of tooth-inducing cell populations is an

236 nclude skewing of regulatory over effector T cells, expansion of regulatory T-cell subsets expressing

237 ector memory T cells and IL17A+ T-regulatory cells; expansion of HLA-DR+CD56+ granulocytes; and reduc

238 so accounts for the observed dependence of T cell expansion on affinity for antigen and on the kineti

239 ntrinsic manner without disrupting Ag-driven cell expansion or effector function.

240 rocesses during plant development, including cell expansion, organ initiation, and cell separation.

241 ermissive environment favoring leukemic stem cell expansion over normal HSC maintenance, and evidence

242 In addition to promoting B cell expansion, overexpression of BAFF promotes expansio

243 le deposition during the early stages of the cell expansion period by incorporating additional cutin

244 ell numbers typically improve while CD8(+) T-cell expansion persists, and both CD4(+) T-cell cytopeni

245 vCEB1(opt) ) from wine grape involved in the cell expansion phase of berry development.

246 ion of TOR is concomitant with alteration of cell expansion, proliferation and specialized metabolism

247 The promotive effect of auxin on shoot cell expansion provided the bioassay used to isolate thi

248 ray organization and dynamics with degree of cell expansion, quantitative imaging tools established b

249 We found that tuft cell expansion reduced chronic intestinal inflammation i

250 Here, we find that active surface cell expansion represents the key process coordinating t

251 Cell expansion requires that ion transport and secretory

252 nversely curbs tumour growth and cancer stem cell expansion, restores chemosensitivity and blocks met

253 or role in membrane fusion and contribute to cell expansion, signaling, and polar growth in plants.

254 levation of plasma glucagon levels and alpha-cell expansion similar to wild-type mice.

255 est known to induce CD25(+) regulatory CD4 T cell expansion, surprisingly causes robust induction of

256 the Morrbid RNA and its locus control CD8 T cell expansion, survival, and effector function by regul

257 temporal controls of cell proliferation and cell expansion sustain differential growth that defines

258 that the STING N153S mutation caused myeloid cell expansion, T cell cytopenia, and dysregulation of i

259 unotherapies that improve antigen-specific T cell expansion, T regulatory cell depletion, or effector

260 have a greater requirement for GA to promote cell expansion than the lower embryo axis.

261 a result of exaggerated polyfunctional Th22-cell expansion that was reversed by IL-22 deletion or IL

262 nical CMV reactivation drives CD4+CD28null T-cell expansion, that this is associated with impaired im

263 Later on, during cell expansion, the plasmodesmata pore widens and the tw

264 s that FRCs play a role beyond restricting T cell expansion-they can also shape the fate and function

265 also the potential for pancreatic islet beta-cell expansion through c-MET regulation to ameliorate be

266 L) is a chronic disease resulting in myeloid cell expansion through expression of the BCR-ABL1 fusion

267 uction, together with the inhibition of CK5+ cell expansion through RAR/PR cross talk, may explain th

268 /NAC1L-EXPA2 network in regulating endosperm cell expansion to control the seed-to-seedling transitio

269 pDCs and microbial colonization induce T reg cell expansion to protect against severe bronchiolitis a

270 osynthesis, thereby facilitating anisotropic cell expansion to ultimately form the heart-shaped Capse

271 action, VEGFA upregulates Sox2 to drive stem cell expansion, together with miR-452 loss and Slug upre

272 lete loss of CD137 expression and impaired T cell expansion toward CD137 ligand-expressing cells.

273 r through multiple strategies including stem cell expansion, transdifferentiation, or proliferation o

274 show that defects in both cell division and cell expansion underlie the dwarfism of an Arabidopsis l

275 ated the competing effects of drug-resistant cell expansion versus overall tumor regression as a func

276 D70 expression in T cells, and CD70 limits T cell expansion via a regulatory T cell-independent mecha

277 contraction via actomyosin cytoskeleton and cell expansion via cell-cell adhesion.

278 cross-linking, lignification and, possibly, cell expansion via H(2) O(2) -derived hydroxyl radicals.

279 enetic support for SAUR-PP2C.D regulation of cell expansion via modulation of PM H(+)-ATPase activity

280 es the growth of plant shoots by stimulating cell expansion via plasma membrane (PM) H(+)-ATPase acti

281 CAR T-cell expansion was associated with responses, and CAR T

282 atural cross-linking surface and that T(reg) cell expansion was independent of the antibody Fc region

283 In addition, T(reg) cell expansion was not increased by adding either supple

284 sulinomas hold the "genomic recipe" for beta cell expansion, we surveyed 38 human insulinomas to obta

285 , a cytotoxic immune response and a clonal T-cell expansion were not observed in the tumors or periph

286 e patients (n = 24), response and peak CAR T-cell expansion were superior in the HD-Cy/MRD cohorts, a

287 dicate that no JCV-related specific T- and B-cell expansions were mounted at the time of PML.

288 , 12, and 24 mo), posttransplant NKG2C(+) NK cell expansions were not observed in every patient with

289 nthesis is a critical failsafe that prevents cell expansion when light and nutrients are plentiful, b

290 (RALFs), regulate plant immune responses and cell expansion, which are two important factors for succ

291 lization as the trigger for transitioning to cell expansion, which drives postfertilization fruit gro

292 assays showed no donor-specific regulatory T cell expansion, which has been consistently observed in

293 High temperature promotes guard cell expansion, which opens stomatal pores to facilitate

294 ytotoxic, inflammatory cytokine immunity, to cell expansion with diminished cytokine but increased co

295 ungal hyphae, possess a typical tip or polar cell expansion with growth limited to the apical dome.

296 une deficiency (biallelic null mutations), B-cell expansion with nuclear factor kappaB and T-cell ane

297 onresponders displayed dramatic pretherapy T cell expansions with minimal change following ACT.

298 A recent report demonstrates clonal T cell expansion within neurogenic niches of the aged brai

299 ing factor neutralization inhibited DC and T-cell expansion within pericardial AT, and translated int

300 teractions of PD-L1 with CD80 augment CD8+ T cell expansion without increasing anergy, exhaustion, or