ライフサイエンスコーパス: costimulation blockade

1 ipheral transplantation tolerance induced by costimulation blockade.

2 tion of transplantation tolerance induced by costimulation blockade.

3 ss resist prolongation of skin allografts by costimulation blockade.

4 allograft survival was readily prolonged by costimulation blockade.

5 of sublethally irradiated mice treated with costimulation blockade.

6 es some of the survival advantage induced by costimulation blockade.

7 T cell apoptotic pathway, on the effects of costimulation blockade.

8 l for the induction of hyporesponsiveness by costimulation blockade.

9 opoietic chimerism, lymphocyte depletion and costimulation blockade.

10 lanted tissues when induced by coreceptor or costimulation blockade.

11 r saturation as a pharmacodynamic measure of costimulation blockade.

12 partial regimens, or a full regimen based on costimulation blockade.

13 tic and skin allografts in mice treated with costimulation blockade.

14 dramatically prolonged graft survival under costimulation blockade.

15 slet allograft survival in mice treated with costimulation blockade.

16 deficient mice show early graft loss despite costimulation blockade.

17 for long-term allograft survival induced by costimulation blockade.

18 skin allograft survival in mice treated with costimulation blockade.

19 ection driven by CD8(+) T cells resistant to costimulation blockade.

20 llograft survival in recipients treated with costimulation blockade.

21 graft survival was compared in untreated and costimulation blockade (500 microg anti-CD40L and 500 mi

22 - mice than in IFN-gamma+/+ mice, and T-cell costimulation blockade abrogated alloantigen-induced T-c

23 by treating mice with either B7-CD28 T-cell costimulation blockade alone or B7-CD28 T-cell costimula

24 -/-) mice treated with either B7-CD28 T-cell costimulation blockade alone or B7-CD28 T-cell costimula

25 we find that the full tolerance regimen, or costimulation blockade alone, specifically inhibits alre

26 graft survival beyond that in mice receiving costimulation blockade alone.

27 Late costimulation blockade also reduced virus-specific T-cel

28 neutralizing IL-4 in addition to CD40-CD154 costimulation blockade and CD8+ T-cell depletion prevent

29 ng protocol with ABT-737 in combination with costimulation blockade and low-dose cyclosporine A resul

30 cy may be a valid pharmacodynamic measure of costimulation blockade and provide the first direct clin

31 Combined use of costimulation blockade and rapamycin may provide a means

32 Costimulation Blockade and Sirolimus (CoBS) resulted in

33 etermined the effect that CD28/CD40-directed costimulation blockade and sirolimus have on this diseas

34 ce immunosuppression with CD28/CD40-directed costimulation blockade and sirolimus.

35 gate the role of innate immunity, mice given costimulation blockade and skin allografts were coinject

36 te induction of transplantation tolerance by costimulation blockade and that IL-2/Idd3 is a critical

37 stem cell transplantation protocols based on costimulation blockade and tolerance induction may requi

38 We took cell/complement depletion, costimulation blockade, and serum transfer approaches to

39 ed strategy using a single dose of busulfan, costimulation blockade, and T cell-depleted donor bone m

40 C57BL/6 mice treated with costimulation blockade are able to generate allospecific

41 s, rather than exerting immune modulation by costimulation blockade as currently postulated.

42 t a donor-specific CD8 T cell response under costimulation blockade as well as for the graft to survi

43 ansion and combinatorial therapy with novel, costimulation blockade-based immunosuppression strategie

44 ed-efficacy as in young recipients employing costimulation blockade-based or T-cell depletion-based c

45 urmount these impediments, we have adapted a costimulation blockade-based protocol developed for soli

46 gents currently available, in particular, by costimulation blockade-based regimens.

47 roduction may represent an important part of costimulation blockade-based strategies to promote allog

48 However, costimulation blockade-based tolerance protocols have fa

49 an attractive substitute in mouse models of costimulation blockade-based tolerance regimens.

50 In contrast, following treatment with costimulation blockade, busulfan, and bone marrow, heart

51 bed a nonirradiation-based regimen combining costimulation blockade, busulfan, and donor bone marrow

52 in chemically diabetic NOD mice treated with costimulation blockade but is prolonged further in NOD I

53 previously reported that continuous 24-month costimulation blockade by abatacept significantly slows

54 that TLR signaling abrogates the effects of costimulation blockade by preventing alloreactive CD8+ T

55 These results demonstrate that costimulation blockade can induce hyporesponsiveness of

56 Rapamycin together with costimulation blockade can induce tolerance in organ all

57 It has been reported that costimulation blockade can result in T cell anergy.

58 d depletion of CD4 and/or CD8 pos T cells or costimulation blockade can substitute for ALS and preser

59 ells (Tmem), particularly those resistant to costimulation blockade (CB), are a major barrier to tran

60 c process dependent on the level of residual costimulation blockade, CD4+ regulatory cells, and activ

61 In synchimeric mice treated with costimulation blockade, coadministration of all four TLR

62 Belatacept, a B7-specific mediator of costimulation blockade (CoB), is clinically indicated as

63 stimulation blockade alone or B7-CD28 T-cell costimulation blockade combined with donor splenocyte tr

64 stimulation blockade alone or B7-CD28 T-cell costimulation blockade combined with donor splenocyte tr

65 th on IFN-gamma-deficient recipients despite costimulation blockade could be explained by the lack of

66 ly tolerized by either rapamycin or combined costimulation blockade (CTLA-4Ig plus anti-CD40L mAb).

67 Mice receiving costimulation blockade (CTLA4-Ig and anti-CD40 ligand) a

68 tive preconditioning (low-dose busulfan) and costimulation blockade (CTLA4-Ig and anti-CD40L) to prod

69 NOD.B6 Idd3 mice treated with costimulation blockade deleted alloreactive CD8 T-cells

70 ntribution of Tregs to immune suppression by costimulation blockade depends on the concentration of C

71 from diabetes by a short course of combined costimulation blockade, despite the continued diabetogen

72 mice with very severe diabetes treated with costimulation blockade did not reverse diabetes, showing

73 llograft-protective effects of CD40-directed costimulation blockade do not require sCD154 blockade, c

74 Because costimulation blockade does not result in universal tole

75 CD28 and CD40L costimulation blockade during acute infection also dimin

76 monoclonal antibody-mediated coreceptor and costimulation blockade enables long-term engraftment and

77 N-gamma+/+ and IFN-gamma-/- mice, and T-cell costimulation blockade enhanced alloantigen-induced T-ce

78 gld mice treated with costimulation blockade enjoy a significantly greater inc

79 The data also suggest that B7-CD28 T-cell costimulation blockade exerts immunosuppressive actions

80 e almost completely protected from diabetes, costimulation blockade failed to prolong skin allograft

81 Costimulation blockade fails to prolong skin allograft s

82 cy of Th17 cells and conferred resistance to costimulation blockade following transplantation.

83 Costimulation blockade has been shown to be effective in

84 T cell costimulation blockade has shown promise as an alternati

85 ne or rapamycin were compared as adjuncts to costimulation blockade in the murine BALB/c to C3H/He he

86 intenance of allograft protection induced by costimulation blockade in this model.

87 d transplantation, where treatments based on costimulation blockade, in particular CD40 ligand (CD40L

88 linated neoantigens and clinical efficacy of costimulation blockade indicate a general defect in main

89 asL is not required for the establishment of costimulation blockade induced hyporesponsiveness, but r

90 Surprisingly, costimulation blockade induced permanent islet allograft

91 Deletion of CD4 or CD25 cells during costimulation blockade induced rapid rejection of skin b

92 human autoimmune diabetes, are resistant to costimulation blockade-induced allograft tolerance.

93 This study demonstrated that short-term costimulation blockade-induced dominant tolerance and th

94 e role of Foxp3 regulatory T (Treg) cells in costimulation blockade-induced dominant tolerance to por

95 Strain differences in costimulation blockade-induced hyporesponsiveness persis

96 sis that NOD mice would also be resistant to costimulation blockade-induced rat xenograft tolerance.

97 nity and that autoimmunity and resistance to costimulation blockade-induced transplantation tolerance

98 Costimulation blockade induces prolonged rat islet and s

99 e and rapamycin may provide a means to bring costimulation blockade into the clinic.

100 closporine and rapamycin upon the outcome of costimulation blockade is forwarded.

101 In contrast, costimulation blockade is ineffective in this clinically

102 of NOD mice to resist tolerance induction by costimulation blockade is mediated by both CD4+ and CD8+

103 hematopoietic chimerism in mice treated with costimulation blockade is not known.

104 ft survival in NOD.B6 Idd3 mice treated with costimulation blockade is prolonged compared with NOD mi

105 The alloresponse suppressed by costimulation blockade is restored by LCMV infection and

106 vival in (NOD x C57BL/6)F1 mice treated with costimulation blockade is short, suggesting a strong gen

107 cipients with anti-CD40 ligand and CTLA-4Ig (costimulation blockade) is a powerful promising albeit n

108 After costimulation blockade, islet allograft survival was pro

109 Moreover, short-term costimulation blockade led to robust immune tolerance th

110 er the diagnosis of type 1 diabetes and that costimulation blockade may exert its beneficial therapeu

111 Here we demonstrate that costimulation blockade-mediated tolerance after lung tra

112 hypothesize that CD8(+) T cell "escape" from costimulation blockade might be a IL-15/IL-15R dependent

113 olerance, we hypothesized that "escape" from costimulation blockade might represent a CD8(+) and IL-1

114 s with conventional agents (n=3) or based on costimulation blockade (n=7).

115 In murine models, T-cell costimulation blockade of the CD28:B7 and CD154:CD40 pat

116 Costimulation blockade of the CD40/CD154 pathway has bee

117 erefore, besides direct inhibition of T-cell costimulation, blockade of B7/CD28 may facilitate induct

118 Costimulation blockade or gene knockout of either CD28 o

119 depleting mechanism of action and not merely costimulation blockade plays a substantial role in the t

120 .TNFR2-/- and B6.IL-12R-/- mice treated with costimulation blockade plus LPS also exhibited short ski

121 oncytotoxic, irradiation-free approach using costimulation blockade plus rapamycin treatment.

122 ovide insight into potential risks following costimulation blockade posed by chronic or latent viral

123 Importantly, costimulation blockade prevented the rejection of alloge

124 lycytidylic acid (TLR3) to mice treated with costimulation blockade prevents alloreactive CD8(+) T ce

125 Costimulation blockade prolonged skin allograft survival

126 Although CD154 costimulation blockade prolongs allograft survival in mu

127 Using a costimulation blockade protocol based on a donor-specifi

128 We used a costimulation blockade protocol consisting of a donor-sp

129 Costimulation blockade protocols are effective in prolon

130 ection, recipients treated with a CD28-CD154 costimulation blockade regimen achieved sustained insuli

131 Fas expression is not critical for costimulation blockade resistant rejection, suggesting t

132 but rather appears to be required for normal costimulation blockade resistant rejection.

133 resents a new and potent strategy to prevent costimulation blockade-resistant CD8(+) T cell-driven re

134 IL-6 ablated the Th17 response and reversed costimulation blockade-resistant graft rejection.

135 We have previously shown that the costimulation blockade-resistant phenotype can be attrib

136 in cells of hemopoietic origin and that the costimulation blockade-resistant phenotype is dominant.

137 A-1-specific induction therapy to neutralize costimulation blockade-resistant populations of T cells

138 Costimulation blockade-resistant rejection (CoBRR) is as

139 nfection, but, strikingly, failed to mediate costimulation blockade-resistant rejection after challen

140 To elucidate the mechanisms of costimulation blockade-resistant rejection and to improv

141 he ability of donor-reactive Tmem to mediate costimulation blockade-resistant rejection during a reca

142 is study, we report that CD8(+) Th17 mediate costimulation blockade-resistant rejection in T-bet(-/-)

143 We hypothesize that the costimulation blockade-resistant rejection mediated by L

144 jection, these approaches fail, resulting in costimulation blockade-resistant rejection.

145 ng rejection and suggest a strategy to avoid costimulation blockade-resistant rejection.

146 +) CD8(+) cells play a critical role in this costimulation blockade-resistant rejection.

147 gesting a link between CD28-negative Tem and costimulation blockade-resistant rejection.

148 kthrough response temporally correlated with costimulation blockade-resistant rejection.

149 CD8 T cells are necessary for costimulation blockade-resistant rejection.

150 memory T (TM) cells have been implicated in costimulation blockade-resistant transplant rejection, d

151 To determine whether the costimulation blockade resulted in tolerance, adult-thym

152 When mice were treated with costimulation blockade, reversal of diabetes was observe

153 r of NF-kappa B translocation, together with costimulation blockade, synergistically impairs memory T

154 y) total body irradiation and treatment with costimulation blockade, T-cell depletion, or rapamycin.

155 nd support further investigation of combined costimulation blockade targeting the CD28 and CD40 pathw

156 ration occurred in protected recipients, yet costimulation blockade temporarily blunted early T-cell

157 ival of skin allografts in mice treated with costimulation blockade through a CD8 T cell-dependent, M

158 treatment drastically blunts the ability of costimulation blockade to produce long-term engraftment.

159 cyclosporine therapy blocked the capacity of costimulation blockade to produce permanent engraftment,

160 rlying mechanisms, we studied the ability of costimulation blockade to prolong islet allograft surviv

161 ermanent engraftment, combined rapamycin and costimulation blockade treatment produced permanent engr

162 strain combination known to be refractory to costimulation blockade treatment, combined treatment wit

163 vented in the early posttransplant period by costimulation blockade using CD154 or anti-inducible cos

164 aft tolerance in mice induced through either costimulation blockade using CD154-specific antibody the

165 ipheral transplantation tolerance induced by costimulation blockade using donor-specific transfusion

166 depletion in (NOD x CBA)F1 mice treated with costimulation blockade was impaired compared with simila

167 In this model, donor cell infusion and costimulation blockade without busulfan were insufficien

168 cluding short-term depleting anti-CD4 mAb or costimulation blockade, would affect the disease progres