TY - JOUR
T1 - Site-specific control of T cell traffic in the brain
T2 - T cell entry to brainstem vs. hippocampus after local injection of IFN-γ
AU - Phillips, Lynnette M.
AU - Lampson, Lois A.
N1 - Funding Information:
This work was supported by funds from NINDS (NS29510) to L.A.L., and by fellowship support to L.M.P. from the National Multiple Sclerosis Society (FG1213) and NIH (MH11612).
PY - 1999/5/3
Y1 - 1999/5/3
N2 - Although it is known that neurotransmitters and neuropeptides can affect immune function in vitro, less is understood about how the neural environment affects immune function in the brain. Previously, we showed that regulation of parenchymal class II MHC after local injection of IFN-γ is site-specific. In this companion study, we defined the effect of local IFN-γ on the entry of class II-restricted T cells to the brain parenchyma. To activate endogenous T cells, adult CDF rats were immunized with a normal neural antigen (MBP). Two weeks later, the proinflammatory cytokine IFN-γ (100 to 10,000 U/site) was injected stereotaxically into two neurochemically and anatomically distinct sites, the hippocampus (area CA1) and brainstem (nucleus of the solitary tract). Monoclonal R73 was used to detect T cells on cryostat sections. The greatest difference was seen 48 h after 300 U IFN-γ was injected at each site, when there were several-fold more parenchymal T cells in the brainstem than in the hippocampus. Most parenchymal T cells were CD4+/class II-restricted. Thus, parenchymal T cell entry and parenchymal class II up-regulation show the same hierarchy (brainstem >> hippocampus) after local IFN-γ injection, although T cell entry was more sensitive to the IFN-γ dose. We suggest that the local regulatory environment contributes to site-specific immune regulation, and discuss implications for the distribution of MS plaques and other aspects of local immune control. Further, in interpreting the many previous studies of cytokine-mediated immune changes in the CNS, the possibility of site-specific differences should be considered.
AB - Although it is known that neurotransmitters and neuropeptides can affect immune function in vitro, less is understood about how the neural environment affects immune function in the brain. Previously, we showed that regulation of parenchymal class II MHC after local injection of IFN-γ is site-specific. In this companion study, we defined the effect of local IFN-γ on the entry of class II-restricted T cells to the brain parenchyma. To activate endogenous T cells, adult CDF rats were immunized with a normal neural antigen (MBP). Two weeks later, the proinflammatory cytokine IFN-γ (100 to 10,000 U/site) was injected stereotaxically into two neurochemically and anatomically distinct sites, the hippocampus (area CA1) and brainstem (nucleus of the solitary tract). Monoclonal R73 was used to detect T cells on cryostat sections. The greatest difference was seen 48 h after 300 U IFN-γ was injected at each site, when there were several-fold more parenchymal T cells in the brainstem than in the hippocampus. Most parenchymal T cells were CD4+/class II-restricted. Thus, parenchymal T cell entry and parenchymal class II up-regulation show the same hierarchy (brainstem >> hippocampus) after local IFN-γ injection, although T cell entry was more sensitive to the IFN-γ dose. We suggest that the local regulatory environment contributes to site-specific immune regulation, and discuss implications for the distribution of MS plaques and other aspects of local immune control. Further, in interpreting the many previous studies of cytokine-mediated immune changes in the CNS, the possibility of site-specific differences should be considered.
KW - Experimental autoimmune encephalomyelitis (EAE)
KW - Myelin basic protein (MBP)
KW - Neuroimmunology
KW - Rat
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U2 - 10.1016/S0165-5728(99)00034-X
DO - 10.1016/S0165-5728(99)00034-X
M3 - Article
C2 - 10337920
AN - SCOPUS:0033519331
SN - 0165-5728
VL - 96
SP - 218
EP - 227
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 2
ER -