Immunological aspects of grafting in the mammalian central nervous system. A review and speculative synthesis

Widner, Håkan; Brundin, Patrik

doi:10.1016/0165-0173(88)90010-0

Cited by 283 publications

(78 citation statements)

References 185 publications

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“…The concept of the immunologically privileged status of the brain refers to the empirical finding that allogeneic or xenogeneic tissues exhibit a prolonged survival, or a higher rate of survival after a given time, when grafted into the brain parenchyma in comparison with those grafted to peripheral sites (Widner and Brundin 1988). This does not mean that immune reactions cannot take place in the brain.…”

Section: Discussionmentioning

confidence: 99%

The Generation of Macrophages from Precursor Cells Incubated with Brain Endothelial Cells. A Release of CSF-l Like Factor from Endothelial Cells.

Tanaka¹,

Kishi

McCarron

et al. 1993

Tohoku J. Exp. Med.

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Section: Discussionmentioning

confidence: 99%

The Generation of Macrophages from Precursor Cells Incubated with Brain Endothelial Cells. A Release of CSF-l Like Factor from Endothelial Cells.

Tanaka¹,

Kishi

McCarron

et al. 1993

Tohoku J. Exp. Med.

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“…The privileged status of the brain is now regarded as the result of a balance of regulated events that produces either immune privilege or effective responses. 4,5 In terms of neural grafting, there are several factors that contribute to the timing and intensity of the rejection response and this includes the type of graft transplanted, the degree of immunological disparity between donor and recipient, and how and where the tissue is implanted.…”

Section: The Brain As a Transplantation Sitementioning

confidence: 99%

Immune problems in central nervous system cell therapy

Barker¹,

Widner

2004

Neurotherapeutics

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173

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Summary:Transplantation of cells and tissues to the mammalian brain and CNS has revived the interest in the immunological status of brain and its response to grafted tissue. The previously held view that the brain was an absolute "immunologically privileged site" allowing indefinite survival without rejection of grafts of cells has proven to be wrong. Thus, the brain should be regarded as a site where immune responses can occur, albeit in a modified form, and under certain circumstances these are as vigorous as those seen in other peripheral sites. Clinical cell transplant trials have now been performed in Parkinson's disease, Huntington's disease, demyelinating diseases, retinal disorders, stroke, epilepsy, and even deafness, and normally are designed as cell replacement strategies, although implantation of genetically modified cells for supplementation of growth factors has also been tried. In addition, some disorders of the CNS for which cell therapies are being considered have an immunological basis, such as multiple sclerosis, which further complicates the situation. Embryonic neural tissue allografted into the CNS of animals and patients with neurodegenerative conditions survives, makes and receives synapses, and ameliorates behavioral deficits. The use of aborted human tissue is logistically and ethically complicated, which has lead to the search for alternative sources of cells, including xenogeneic tissue, genetically modified cells, and stem cells, all of which can and will induce some level of immune reaction. We review some of the immunological factors involved in transplantation of cells to CNS.

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“…The brain is considered to be an immunologically privileged site where immune reactions are more restricted than in the rest of the body [13]. There are several contributing factors, including unconventional lymphatic drainage and possibly less effective antigen presentation in the brain, but grafts placed in the brain parenchyma do immunize recipients.…”

Section: Introductionmentioning

confidence: 99%

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

Larsson

Corbascio

Widner

et al. 2002

Xenotransplantation

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: 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, CTLA4Ig 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 CTLA4Ig 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.

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Immunological aspects of grafting in the mammalian central nervous system. A review and speculative synthesis

Cited by 283 publications

References 185 publications

The Generation of Macrophages from Precursor Cells Incubated with Brain Endothelial Cells. A Release of CSF-l Like Factor from Endothelial Cells.

The Generation of Macrophages from Precursor Cells Incubated with Brain Endothelial Cells. A Release of CSF-l Like Factor from Endothelial Cells.

Immune problems in central nervous system cell therapy

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

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