PMID- 8813361
OWN - NLM
STAT- MEDLINE
DCOM- 19961218
LR  - 20190614
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 722
IP  - 1-2
DP  - 1996 May 25
TI  - Interactions of neurotrophic factors GDNF and NT-3, but not BDNF, with the immune 
      system following fetal spinal cord transplantation.
PG  - 153-67
AB  - Glial cell line-derived neurotrophic factor (GDNF) is known to stimulate survival 
      of dopaminergic and spinal cord motor neurons. However, little is known of the 
      possible immune sequelae of GDNF exposure, or that of other putative trophic 
      factors. To address these questions we utilized in oculo grafts of spinal cord, 
      wherein we could induce different levels of immune responses via allogeneic vs. 
      syngeneic combinations. Adult female Sprague-Dawley and Fisher rats were used as 
      hosts for allogeneic and syngeneic grafts, respectively. Embryonic age 
      14-15-day-old fetuses were taken from pregnant dams of each strain, and cervical 
      spinal cords were removed and dissected. Pieces of the spinal cord were 
      transplanted into the anterior chamber of the eye within each strain. At 5-day 
      intervals, 0.5 microgram of GDNF, brain-derived neurotrophic factor (BDNF), 
      neurotrophin-3 (NT-3) or cytochrome c (CC) was injected into the anterior chamber 
      of the eye and the sizes of the transplants were measured for the Sprague-Dawley 
      rats. The same injections and measurements, but only for GDNF and CC, were 
      carried out using Fisher rats. As expected, GDNF increased transplant survival 
      and growth in both the Sprague-Dawley and Fisher animals. At day 41-42, all rats 
      were sacrificed. Cameral graft appearance was evaluated by cresyl violet and 
      immunohistochemically using antibodies against neurofilament (NF), calcitonin 
      gene-related peptide (CGRP) and glial fibrillary acidic protein (GFAP). To 
      monitor immune responses, the following monoclonal antibodies were used: OX38 
      against CD4, OX18 against MHC class I (MHCI), OX8 against CD8, OX6 against MHC 
      class II (MHCII), OX42 against CD11b, R73 against alpha and beta T cell receptor 
      (TcR), and ED1. In the Sprague-Dawley grafts, significantly higher amounts of 
      CD8+, T lymphocyte+, MHCI+ and MHCII+ antigen-presenting cells (APC) were 
      observed in GDNF-treated transplants. These markers were also increased in 
      NT-3-treated groups. There were two types of OX-42+ cells, one was the ordinary 
      ramified microglial cell, the other appeared to be a phagocytic cell, looking 
      like the interstitial proliferating variety. Interestingly, the phagocytic OX-42+ 
      cells had the same distribution as ED1+ and MHCII+ cells. In contrast, there were 
      few immunoreactive cells after GDNF treatment in the inbred Fisher animals, 
      similar to the CC control group. These results suggest that GDNF and to some 
      extent NT-3, can activate the immune system in allogeneic graft combinations, but 
      that these trophic factors do not produce overt rejection, and do not per se 
      induce immune responses.
FAU - Shinoda, M
AU  - Shinoda M
AD  - Department of Neuroscience, Berzelius Laboratory, Karolinska Institute, 
      Stockholm, Sweden.
FAU - Hoffer, B J
AU  - Hoffer BJ
FAU - Olson, L
AU  - Olson L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Gdnf protein, rat)
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Neurotrophin 3)
RN  - 0 (OX-38 monoclonal antibody)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/immunology
MH  - Brain-Derived Neurotrophic Factor/*physiology
MH  - Embryonic and Fetal Development
MH  - *Fetal Tissue Transplantation
MH  - Glial Cell Line-Derived Neurotrophic Factor
MH  - Immune System/*physiology
MH  - Male
MH  - Microglia/cytology
MH  - Nerve Growth Factors/*physiology
MH  - Nerve Tissue Proteins/*physiology
MH  - Neuroprotective Agents/*metabolism
MH  - Neurotrophin 3
MH  - Ophthalmologic Surgical Procedures
MH  - Postoperative Period
MH  - Rats
MH  - Rats, Inbred F344
MH  - Rats, Sprague-Dawley
MH  - Spinal Cord/cytology/*embryology
EDAT- 1996/05/25 00:00
MHDA- 1996/05/25 00:01
CRDT- 1996/05/25 00:00
PHST- 1996/05/25 00:00 [pubmed]
PHST- 1996/05/25 00:01 [medline]
PHST- 1996/05/25 00:00 [entrez]
AID - 0006-8993(96)00208-9 [pii]
AID - 10.1016/0006-8993(96)00208-9 [doi]
PST - ppublish
SO  - Brain Res. 1996 May 25;722(1-2):153-67. doi: 10.1016/0006-8993(96)00208-9.