ライフサイエンスコーパス: LT-alpha

1 LT alpha also induced chemokine protein within 8 h of tr

2 LT alpha exists in its soluble form as a homotrimer, whi

3 LT alpha induces inflammation at the sites of expression

4 LT alpha-/- mice immunized with low doses of (4-hydroxy-

5 LT alpha-deficient mice and LT beta R-Fc transgenic mice

6 LT-alpha has AP-2, Ets, NF-kappaB, SP-1 and STAT binding

7 LT-alpha(-/-) HEVs had no PNAd, HEC-6ST, or GlyCAM-1.

8 LT-alpha-/- mice were primed so that their splenic lymph

9 on of proinflammatory factors (IL-15, IL-12, LT-alpha, LT-beta, TNF-alpha, RANTES) which is coinciden

10 bvious role for TNFR2, since in its absence, LT alpha-induced inflammation is quantitatively and qual

11 type mice, reduced (LT-beta(-/-)) or absent (LT-alpha(-/-)) lymphoid chemokines, and no T- and B-cell

12 Lymphotoxin alpha (LT alpha)-deficient mice revealed critical roles for LT

13 Although lymphotoxin-alpha (LT alpha) has been shown to be required for normal lymph

14 Lymphotoxin-alpha (LT alpha) has recently been demonstrated to be important

15 Human lymphotoxin-alpha (LT alpha) is found in a secreted form and on the surface

16 for six biallelic TNF and lymphotoxin-alpha (LT alpha) polymorphisms and eight class I and II HLA loc

17 Mice deficient in lymphotoxin-alpha (LT alpha-/- mice) have no lymph nodes or Peyer's patches

18 l centers is dependent on lymphotoxin alpha (LT-alpha) and LT-beta signaling components.

19 mice deficient in either lymphotoxin alpha (LT-alpha) or type I tumor necrosis factor receptor (TNFR

20 We identify surface lymphotoxin-alpha (LT-alpha) as common to T(H)0, T(H)1 and T(H)17 cells and

21 mice deficient in either lymphotoxin-alpha (LT-alpha) or the type I tumor necrosis factor (TNF) rece

22 associated factor family, lymphotoxin-alpha (LT-alpha), and a membrane-associated protein referred to

23 LT) protein complex is a heteromer of alpha (LT-alpha, also called tumor necrosis factor (TNF)-beta)

24 Using lymphotoxin-alpha-(LT-alpha)-, TNF-alpha-, or TNFRp55-deficient mice, all w

25 clear whether LT alpha functions through an LT alpha homotrimer (LT alpha3) or LT alpha/beta heterot

26 ersion of mLT beta in insect cells led to an LT alpha beta form that was cytotoxic in the WEHI 164 as

27 ss, we examined LT alpha-/- mice in which an LT alpha transgene under the control of the rat insulin

28 The LT alpha+250 and LT alpha+250G/TNF-308G haplotypes are associated with pr

29 ata highlight distinct roles of LT alpha and LT alpha beta in lymphoid organogenesis supporting the n

30 ed by membrane-bound and soluble LT beta and LT alpha LT beta oligomers.

31 An inhibitor protein of LIGHT and LT alpha beta2 (LT beta R-Ig) and an inhibitor protein o

32 of bone marrow cells from TNF(-/-) mice and LT alpha(-/-) mice was transferred into irradiated LT al

33 These data indicate that LT-alpha(3) and LT-alpha(1)beta(2) cooperatively contribute to NALT deve

34 c polymorphisms in each of the TNF-alpha and LT-alpha genes.

35 LT-beta(-/-) and LT-alpha(-/-) NALTs had fewer cells than those of wild-t

36 urface expression of CD23, ICAM-1, CD80, and LT-alpha in JAK3-deficient patients.

37 and upregulation of CD23, ICAM-1, CD80, and LT-alpha surface expression.

38 The bacterially expressed woodchuck TNF and LT-alpha proteins exhibited cytotoxic activities on both

39 The specific activities of TNF and LT-alpha were 2.62x10(8) units/mg and 2.22x10(3) units/m

40 Cells that bound LT beta R also bound anti-LT alpha and anti-LT beta mAbs in a FACS analysis.

41 3, and/or cell-bound lymphotoxin-alpha beta (LT alpha beta) mediate these developmental events.

42 s factor (TNF) and lymphotoxin-alpha, -beta (LT-alpha, -beta) cDNAs, genes and proteins to facilitate

43 y, a recombinant LT beta R was shown to bind LT alpha LT beta heteromeric complexes.

44 Here we report that blocking LT alpha beta/lymphotoxin-beta receptor (LT beta R) inte

45 Both LT-alpha-/- and TNFR-I-/- mice lacked FDC clusters in LN

46 Interestingly, although both LT-alpha-/- and TNFR-I-/- mice that had been immunized w

47 tion and GC formation are controlled by both LT-alpha-expressing BM-derived cells and by TNFR-I-expre

48 ependent luminal PNAd is under regulation by LT alpha beta.

49 t BP-1 inhibited the interaction of cellular LT-alpha with HveA.

50 The lymphotoxin-alpha beta complex (LT alpha beta) is found on the surface of activated lymp

51 rs in EAE, C57BL/6 mice, LT-alpha-deficient (LT-alpha-/- mice), or LT-beta-deficient (LT-beta-/- mice

52 Lymphotoxin-alpha-deficient (LT-alpha-/-) mice manifest congenital absence of lymph n

53 a hi cells, delivering IL-7R alpha-dependent LT alpha 1 beta 2 signals critical for LN development.

54 Depleting LT-alpha-specific mAb inhibited T cell-mediated models o

55 These data indicate that depleting LT-alpha-expressing lymphocytes with LT-alpha-specific m

56 d the plasticity of the process, we examined LT alpha-/- mice in which an LT alpha transgene under th

57 3- IL-7R alpha hi cells are shown to express LT alpha 1 beta 2 in an IL-7R alpha-dependent manner.

58 rganogenesis, mice simultaneously expressing LT alpha and LT beta under rat insulin promoter II (RIP)

59 )-deficient mice revealed critical roles for LT alpha in lymphoid organogenesis, but it is not clear

60 there are four exons for TNF, four exons for LT-alpha and three exons for LT-beta.

61 Lymphotoxin in its membrane form (LT alpha 1 beta 2 heterotrimer) is required for the deve

62 LT, different sources of T and B cells from LT alpha(-/-) mice or TNF(-/-) mice were used for recons

63 -)) mice that had received spleen cells from LT-alpha-/- mice were immunized with sheep red blood cel

64 Furthermore, LT-alpha -/- mice had a higher incidence and shorter inc

65 +250 site within the lymphotoxin-alpha gene (LT alpha+250) on the risk of prolonged mechanical ventil

66 When mLT alpha, human (h) LT alpha, and mTNF-alpha were compared, mLT alpha was th

67 crosis factor family cytokines, heterotrimer LT alpha 1 beta 2 and homotrimer LIGHT, and activates mu

68 However, LT alpha-/- mice immunized with high doses of NP-OVA, ev

69 However, LT-alpha-/- mice were quite resistant to EAE with low av

70 specific activity relative to that of human LT alpha in the conventional WEHI 164 cytotoxicity bioas

71 Both secreted human LT alpha and TNF have similar biological activities medi

72 ctivity comparable to that of secreted human LT alpha were secreted from primary spleen cells, spleni

73 n molecules; they are the first to implicate LT-alpha(1)beta(2) in GlyCAM-1 regulation in NALT HEV de

74 first to demonstrate reconstitution of LN in LT alpha-/- mice and show that the process of LN restora

75 The LT alpha transgene restored LN in LT alpha-/- mice.

76 ce of cervical and mesenteric lymph nodes in LT alpha-deficient mice, and yet their presence in LT be

77 he secreted LT alpha3 signaling via TNFR1 in LT alpha-induced inflammation, and a separate and distin

78 t unidentified cell found more abundantly in LT-alpha -/- than in LT-beta -/- mice may assist in the

79 restore FDC organization and GC formation in LT-alpha-deficient mice, indicating that formation of th

80 Rarely are mesenteric LNs found in LT-alpha-/- mice.

81 Germinal center formation was restored in LT-alpha-deficient mice by transplantation of normal bon

82 s that anti-dsDNA B cells remain tolerant in LT-alpha(-/-), TNF-alpha(-/-), and TNFRp55(-/-) mice; ho

83 ptor 1 and 2 (CR1/2)-deficient BM cells into LT-alpha-deficient mice.

84 ve cervical and mesenteric lymph nodes, into LT-alpha -/- mice, which do not, did not alter the incid

85 To investigate LT alpha beta's activities in lymphoid organogenesis, mi

86 ha(-/-) mice was transferred into irradiated LT alpha(-/-) mice or TNF(-/-) mice.

87 etween the cell receptor, its natural ligand LT-alpha and gD, the virus-specific protein involved in

88 fere with HveA binding to its natural ligand LT-alpha, we found that BP-1 inhibited the interaction o

89 Lymphotoxin (LT, LT alpha, TNF beta) is a member of the immediate TNF fam

90 ogenesis, we suggest that lymphotoxin's (LT, LT-alpha, TNF-beta) crucial role in these processes is p

91 a recently generated recombinant murine (m) LT alpha preparation were evaluated.

92 of DCs, similar to the mice lacking membrane LT alpha/beta.

93 ividual family members in EAE, C57BL/6 mice, LT-alpha-deficient (LT-alpha-/- mice), or LT-beta-defici

94 a R and TNF-R55 and mAbs specific for murine LT alpha, LT beta, and LT beta R to characterize the app

95 on, yet the biochemical properties of murine LT alpha and LT beta are essentially unknown.

96 The murine LT alpha and LT beta (mLT alpha and mLT beta) proteins h

97 ible to differentiate between the effects of LT alpha NcoI and TNF-308 alleles.

98 surface form of LT exists as a heteromer of LT alpha and LT beta subunits and this complex specifica

99 omeostasis, and transgenic overexpression of LT alpha 1 beta 2 on B cells leads to expansion of the C

100 To elucidate the role of LT alpha in lymphoid organogenesis and the plasticity of

101 These data highlight distinct roles of LT alpha and LT alpha beta in lymphoid organogenesis sup

102 B cells are a key source of LT alpha 1 beta 2 for splenic DC homeostasis, and transg

103 preventive and therapeutic administration of LT-alpha-specific mAb inhibited disease, and immunoablat

104 face complex was produced by coexpression of LT-alpha and a converted form of LT-beta wherein the nor

105 lymphotoxin (LT) is a heteromeric complex of LT-alpha and LT-beta chains that binds to the LT-beta re

106 FDCs in SCID mice, even after cotransfer of LT-alpha+/+ T cells.

107 Thus, expression of LT-alpha in the BM-derived cells, but not in the non-BM-

108 These data implicate T cell production of LT-alpha in MOG EAE and support a major role for LT-alph

109 We investigated the role of LT-alpha and TNFR-I in the establishment of spleen FDC a

110 The role of LT-alpha in establishing organized FDC structure was fur

111 hrough an LT alpha homotrimer (LT alpha3) or LT alpha/beta heterotrimers.

112 allele 1 of the LT alpha NcoI polymorphism (LT alpha NcoI*1) (p = 0.005), and allele 2 of the TNF-30

113 Recombinant LT-alpha 1/beta 2 was cytotoxic to the human adenocarcin

114 the mechanisms that reconstitute LN in RIPLT.LT alpha-/- mice.

115 The reconstituted LN of RIPLT.LT alpha-/- mice had germinal center-like peanut aggluti

116 ng dendritic cells was apparent in the RIPLT.LT alpha-/- mice LN.

117 We report here that by the oral route, LT-alpha -/- mice developed scrapie while LT-beta -/- mi

118 ndent on LT-betaR signaling by B cells since LT-alpha-/- B cells are incapable of inducing developmen

119 plenic development, it is unclear if soluble LT alpha 3, and/or cell-bound lymphotoxin-alpha beta (LT

120 the TNF receptors, whereas the cell surface LT alpha beta complex binds to a separate receptor calle

121 R to characterize the appearance of surface LT alpha beta complexes and LT beta R on several common

122 These results demonstrate that surface LT alpha beta ligand plays a critical role in normal lym

123 hat both effects are mediated by the surface LT alpha/beta complex.

124 onoclonal antibody (mAb) directed to surface LT-alpha.

125 We conclude that LT alpha 1 bet a2 acts on DCs or DC precursors to promot

126 Our results indicate that LT alpha-induced inflammation is dependent on the intera

127 These data indicate that LT-alpha(3) and LT-alpha(1)beta(2) cooperatively contrib

128 The LT alpha transgene restored LN in LT alpha-/- mice.

129 The LT alpha+250 and LT alpha+250G/TNF-308G haplotypes are a

130 Although the LT alpha transgene did not restore Peyer's patches or sp

131 GG genotype at the LT alpha+250 site and the LT alpha+250G/TNF-308G haplotype.

132 for patients with a GA or GG genotype at the LT alpha+250 site and the LT alpha+250G/TNF-308G haploty

133 Patients with an AA genotype at the LT alpha+250 site and those without the LT alpha+250G/-3

134 more common in subjects with allele 1 of the LT alpha NcoI polymorphism (LT alpha NcoI*1) (p = 0.005)

135 The association was confined to the LT alpha NcoI*1/TNF-308*2 haplotype, so that it was not

136 the LT alpha+250 site and those without the LT alpha+250G/-308TNFG haplotype had a shorter duration

137 jor role for LT-alpha3, a minor role for the LT-alpha/beta complex, and by inference, no role for TNF

138 ating that these cells were derived from the LT-alpha-deficient recipient.

139 toxin revealed lower cytokine levels in the LT-alpha(-/-) and LT-beta(-/-) NALTs, and undetectable v

140 o form GC were restored, indicating that the LT-alpha-expressing cells required to establish organize

141 n of normal bone marrow, indicating that the LT-alpha-expressing cells required to establish this lym

142 The RNA splicing patterns for TNF, LT-alpha and LT-beta genes are identical among woodchuck

143 to isolate the cDNA and gene clones for TNF, LT-alpha and LT-beta.

144 , humans and mice can differ: the human TNF, LT-alpha and LT-beta genes encode polypeptides of 233, 2

145 o acids respectively, whereas the mouse TNF, LT-alpha and LT-beta genes encode polypeptides of 235, 2

146 overall amino acid sequence homology to TNF, LT-alpha, FasL, and LIGHT, all members of the TNF family

147 The cDNAs for woodchuck TNF, LT-alpha and LT-beta code for proteins of 233, 205 and 3

148 WT T cells transferred EAE to LT-alpha-/- recipients.

149 Unlike LT alpha-deficient mice, LT beta-deficient mice had cerv

150 Furthermore, when LT alpha-/- mice were multiply immunized with high doses

151 When LT-alpha-deficient mice were reconstituted with wild-typ

152 Whereas LT alpha-deficient mice lack all lymph nodes and Peyer's

153 10 are upregulated in p35(-/-) mice, whereas LT-alpha and TNF-alpha levels are reduced.

154 d organogenesis, but it is not clear whether LT alpha functions through an LT alpha homotrimer (LT al

155 d into a secreted form and co-expressed with LT-alpha using baculovirus/insect cell technology.

156 pleting LT-alpha-expressing lymphocytes with LT-alpha-specific mAb may be beneficial in the treatment