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Simultaneous inhibition of B7 and LFA-1 signaling prevents rejection of discordant neural xenografts in mice lacking CD40L.

Larsson, Lena Cecilia LU ; Corbascio, Matthias LU ; Widner, Håkan LU ; Pearson, Thomas C; Larsen, Christian P and Ekberg, Henrik LU (2002) In Xenotransplantation 9(1). p.68-76
Abstract
Transplantation of embryonic human neural tissue can restore dopamine neurotransmission and improve neurological function in patients with Parkinson's disease. Logistical and ethical factors limit the availability of human embryonic allogeneic tissue. Embryonic xenogeneic neural tissue from porcine donors is an alternative form of donor tissue, but effective immunomodulatory techniques are warranted for neural xenotransplantation to become clinically feasible. We transplanted embryonic porcine ventral mesencephalic tissue into the brains of adult untreated C57BL/6 mice, untreated CD40L-/-mice and CD40L-/-mice that received injections of anti-LFA-1, CTLA41g or both compounds. Double-treated CD40L-/-mice had large grafts with high numbers of... (More)
Transplantation of embryonic human neural tissue can restore dopamine neurotransmission and improve neurological function in patients with Parkinson's disease. Logistical and ethical factors limit the availability of human embryonic allogeneic tissue. Embryonic xenogeneic neural tissue from porcine donors is an alternative form of donor tissue, but effective immunomodulatory techniques are warranted for neural xenotransplantation to become clinically feasible. We transplanted embryonic porcine ventral mesencephalic tissue into the brains of adult untreated C57BL/6 mice, untreated CD40L-/-mice and CD40L-/-mice that received injections of anti-LFA-1, CTLA41g or both compounds. Double-treated CD40L-/-mice had large grafts with high numbers of dopaminergic neurons 4 wk after transplantation. The grafts were completely devoid of lymphocytes, macrophages and activated microglia. Untreated C57BL/6 mice had rejected their grafts. Untreated CD40L-/-mice and CD40L-/-mice treated with monotherapy of anti-LFA-1 or CTLA41g had smaller grafts and more microglial and lymphocytic infiltration than double-treated CD40L-/-mice. We conclude that immunomodulation with concomitant inhibition of LFA-1 and B7 signaling in the perioperative period in CD40L-/-mice prevented the rejection of discordant neural xenografts. The treatment most likely reduced antigen presenting capacity and interfered with the costimulatory signaling needed for T cell activation to occur. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Xenotransplantation
volume
9
issue
1
pages
68 - 76
publisher
Wiley-Blackwell
external identifiers
  • wos:000173970800007
  • pmid:12005106
  • scopus:0036461399
ISSN
0908-665X
DOI
10.1034/j.1399-3089.2002.1o010.x
language
English
LU publication?
yes
id
0e45647c-e18a-4872-a68e-ce422c3c4a42 (old id 108153)
date added to LUP
2007-07-16 14:01:32
date last changed
2017-06-04 04:20:49
@article{0e45647c-e18a-4872-a68e-ce422c3c4a42,
  abstract     = {Transplantation of embryonic human neural tissue can restore dopamine neurotransmission and improve neurological function in patients with Parkinson's disease. Logistical and ethical factors limit the availability of human embryonic allogeneic tissue. Embryonic xenogeneic neural tissue from porcine donors is an alternative form of donor tissue, but effective immunomodulatory techniques are warranted for neural xenotransplantation to become clinically feasible. We transplanted embryonic porcine ventral mesencephalic tissue into the brains of adult untreated C57BL/6 mice, untreated CD40L-/-mice and CD40L-/-mice that received injections of anti-LFA-1, CTLA41g or both compounds. Double-treated CD40L-/-mice had large grafts with high numbers of dopaminergic neurons 4 wk after transplantation. The grafts were completely devoid of lymphocytes, macrophages and activated microglia. Untreated C57BL/6 mice had rejected their grafts. Untreated CD40L-/-mice and CD40L-/-mice treated with monotherapy of anti-LFA-1 or CTLA41g had smaller grafts and more microglial and lymphocytic infiltration than double-treated CD40L-/-mice. We conclude that immunomodulation with concomitant inhibition of LFA-1 and B7 signaling in the perioperative period in CD40L-/-mice prevented the rejection of discordant neural xenografts. The treatment most likely reduced antigen presenting capacity and interfered with the costimulatory signaling needed for T cell activation to occur.},
  author       = {Larsson, Lena Cecilia and Corbascio, Matthias and Widner, Håkan and Pearson, Thomas C and Larsen, Christian P and Ekberg, Henrik},
  issn         = {0908-665X},
  language     = {eng},
  number       = {1},
  pages        = {68--76},
  publisher    = {Wiley-Blackwell},
  series       = {Xenotransplantation},
  title        = {Simultaneous inhibition of B7 and LFA-1 signaling prevents rejection of discordant neural xenografts in mice lacking CD40L.},
  url          = {http://dx.doi.org/10.1034/j.1399-3089.2002.1o010.x},
  volume       = {9},
  year         = {2002},
}