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Addition of allogeneic spleen cells causes rejection of intrastriatal embryonic mesencephalic allografts in the rat

Duan, W M LU ; Brundin, P LU and Widner, H LU (1997) In Neuroscience 77(2). p.599-609
Abstract

To address the importance of antigen-presenting cells for the survival of intracerebral neural allografts, allogeneic spleen cells were added to the graft tissue before transplantation. Dissociated embryonic, dopamine-rich mesencephalic and adult spleen tissues were prepared from either inbred Lewis or Sprague-Dawley rats. A mixture of neural and spleen cells was sterotaxically transplanted into the right striatum of adult Sprague-Dawley rats. Controls were neural allografts without addition of allogeneic spleen cells and syngeneic neural grafts with or without the addition of syngeneic spleen cells. Six weeks after transplantation, brain sections were processed immunocytochemically for tyrosine hydroxylase, specific for grafted... (More)

To address the importance of antigen-presenting cells for the survival of intracerebral neural allografts, allogeneic spleen cells were added to the graft tissue before transplantation. Dissociated embryonic, dopamine-rich mesencephalic and adult spleen tissues were prepared from either inbred Lewis or Sprague-Dawley rats. A mixture of neural and spleen cells was sterotaxically transplanted into the right striatum of adult Sprague-Dawley rats. Controls were neural allografts without addition of allogeneic spleen cells and syngeneic neural grafts with or without the addition of syngeneic spleen cells. Six weeks after transplantation, brain sections were processed immunocytochemically for tyrosine hydroxylase, specific for grafted dopamine neurons, and a bank of markers for various components in the immune and inflammatory responses. The neural allografts which were mixed with allogeneic spleen cells were rejected. In these rats, there were high levels of expression of major histocompatibility complex class I and II antigens, intense cellular infiltration including macrophages and activated microglial cells, and a presence of cluster of differentiation 4- and 8-immunoreactive cells in the graft sites. Moreover, there were increased levels of intercellular adhesion molecule-1, tumour necrosis factor-alpha and interleukin-6 in and around the grafts which were undergoing rejection. In contrast, syngeneic neural grafts survived well regardless of whether they were mixed with syngeneic spleen cells or not, and control neural allografts also exhibited unimpaired survival. No significant difference was observed in the number of grafted dopamine neurons among these three latter groups. The levels of expression of the different markers for inflammation and rejection were generally lower in these grafts than in implants of combined allogeneic neural and spleen cells. In summary, intrastriatal neural allografts, which normally survive well in our animal model, were rejected if allogeneic spleen cells from the same donor were added to the graft tissue. The added spleen cells caused strong host immune and inflammatory responses. The study gave support to the notion that immunological privilege of the brain does not provide absolute protection to immunogenetically histoincompatible neural grafts.

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keywords
Animals, Antigen-Presenting Cells, Antigens, CD4, Antigens, CD8, Brain Tissue Transplantation, Cell Transplantation, Female, Fetal Tissue Transplantation, Graft Rejection, Immunohistochemistry, Major Histocompatibility Complex, Mesencephalon, Neostriatum, Rats, Rats, Sprague-Dawley, Receptors, Complement, Spleen, Transplantation, Homologous, Tyrosine 3-Monooxygenase
in
Neuroscience
volume
77
issue
2
pages
11 pages
publisher
Elsevier
external identifiers
  • scopus:0031042628
ISSN
0306-4522
DOI
10.1016/S0306-4522(96)00470-8
language
English
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yes
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bbfbd822-51d5-4973-806a-e70765e7740b
date added to LUP
2017-04-19 18:26:00
date last changed
2017-04-28 12:27:05
@article{bbfbd822-51d5-4973-806a-e70765e7740b,
  abstract     = {<p>To address the importance of antigen-presenting cells for the survival of intracerebral neural allografts, allogeneic spleen cells were added to the graft tissue before transplantation. Dissociated embryonic, dopamine-rich mesencephalic and adult spleen tissues were prepared from either inbred Lewis or Sprague-Dawley rats. A mixture of neural and spleen cells was sterotaxically transplanted into the right striatum of adult Sprague-Dawley rats. Controls were neural allografts without addition of allogeneic spleen cells and syngeneic neural grafts with or without the addition of syngeneic spleen cells. Six weeks after transplantation, brain sections were processed immunocytochemically for tyrosine hydroxylase, specific for grafted dopamine neurons, and a bank of markers for various components in the immune and inflammatory responses. The neural allografts which were mixed with allogeneic spleen cells were rejected. In these rats, there were high levels of expression of major histocompatibility complex class I and II antigens, intense cellular infiltration including macrophages and activated microglial cells, and a presence of cluster of differentiation 4- and 8-immunoreactive cells in the graft sites. Moreover, there were increased levels of intercellular adhesion molecule-1, tumour necrosis factor-alpha and interleukin-6 in and around the grafts which were undergoing rejection. In contrast, syngeneic neural grafts survived well regardless of whether they were mixed with syngeneic spleen cells or not, and control neural allografts also exhibited unimpaired survival. No significant difference was observed in the number of grafted dopamine neurons among these three latter groups. The levels of expression of the different markers for inflammation and rejection were generally lower in these grafts than in implants of combined allogeneic neural and spleen cells. In summary, intrastriatal neural allografts, which normally survive well in our animal model, were rejected if allogeneic spleen cells from the same donor were added to the graft tissue. The added spleen cells caused strong host immune and inflammatory responses. The study gave support to the notion that immunological privilege of the brain does not provide absolute protection to immunogenetically histoincompatible neural grafts.</p>},
  author       = {Duan, W M and Brundin, P and Widner, H},
  issn         = {0306-4522},
  keyword      = {Animals,Antigen-Presenting Cells,Antigens, CD4,Antigens, CD8,Brain Tissue Transplantation,Cell Transplantation,Female,Fetal Tissue Transplantation,Graft Rejection,Immunohistochemistry,Major Histocompatibility Complex,Mesencephalon,Neostriatum,Rats,Rats, Sprague-Dawley,Receptors, Complement,Spleen,Transplantation, Homologous,Tyrosine 3-Monooxygenase},
  language     = {eng},
  number       = {2},
  pages        = {599--609},
  publisher    = {Elsevier},
  series       = {Neuroscience},
  title        = {Addition of allogeneic spleen cells causes rejection of intrastriatal embryonic mesencephalic allografts in the rat},
  url          = {http://dx.doi.org/10.1016/S0306-4522(96)00470-8},
  volume       = {77},
  year         = {1997},
}