Yan-Ling Gao

IL-10 FAILS TO ABROGATE EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS

Mice adoptively‐sensitized to develop chronic relapsing experimental autoimmune encephalomyelitis (EAE), a model for the human demyelinating condition, multiple sclerosis (MS), were given injections of recombinant human IL‐10 at various timepoints post‐sensitization in an attempt to abrogate disease development. IL‐10 is a Th2 immunomodulatory cytokine with known down‐regulatory effects upon Th1 responses and macrophages. Contrary to a previous report on EAE and the predicted outcome, after repeated experiments, IL‐10 was found to elicit a worsening or no effect upon EAE in the mouse. Animals were studied clinically, histopathologically and immunocytochemically. On no occasion was disease ameliorated by IL‐10. Pretreatment with IL‐10 of lymph node cells used to transfer EAE had no effect upon disease outcome, indicating that the cells were already committed effectors. Administration of anti‐IL‐10 monoclonal antibody before onset of signs had no effect when given early post‐sensitization and caused marked worsening when given immediately before onset of signs. In the context of this autoimmune demyelinating model, these results suggest that IL‐10 alone is insufficient to reverse the effector response and indeed may serve to enhance the cascade of events in EAE.

Neuregulin in Neuron/Glial Interactions in the Central Nervous System

Glial growth factor 2 (GGF2) is a neuronal signal that promotes the proliferation and survival of the oligodendrocyte, the myelinating cell of the central nervous system (CNS). This study has focused on recombinant human GGF2 (rhGGF2) and its potential to affect clinical recovery and repair to damaged myelin in chronic relapsing experimental autoimmune encephalomyelitis (EAE) in the mouse, a major animal model for the human demyelinating disease, multiple sclerosis (MS). Mice with EAE were treated with rhGGF2 during both the acute and relapsing phases, and GGF2 treatment led to delayed signs, decreased severity and resulted in statistically significant reductions in relapse rate. Further, rhGGF2-treated groups displayed CNS lesions with more remyelination than in controls. This correlated with increased expression of myelin basic protein exon 2, a marker for remyelination, and with an increase of the regulatory cytokine, IL-10. Thus, a beneficial effect of a neurotrophic growth factor has been demonstrated upon the clinical, pathologic and molecular manifestations of autoimmune demyelination, an effect that was associated with increased expression of a Th2 cytokine. rhGGF2 treatment may represent a novel approach to the treatment of MS (Cannella et al., 1998).

Evidence for γδ T cells with a restricted Vδ6 junctional region in the normal mouse central nervous system

Abstract In this study we present evidence that γδ T cells are present in the normal mouse central nervous system (CNS). Compared with matching spleen γδ T cells, CNS γδ T cells expressed only the CD45RB low phenotype, suggesting that CNS γδ T cells belong to the memory cell population. Approximately 20% expressed exclusively the CD8αβ heterodimer, consistent with a thymic origin. γδ T cells in both spleen and CNS expressed higher levels of the IL-2rβ (CD122), as well as Fas and FasL, than αβ T cells, suggesting that these cells function as immunoregulatory T cells. RT-PCR analysis showed almost exclusive use of Vδ6 in the CNS whereas more Vδ genes were expressed in the spleen. Sequencing of Vδ6 RT-PCR products demonstrated a polyclonal population of T cells in the spleen but a more clonal population within the CNS. The predominant CNS sequence was found in all animals studied and was also detected in the spleen. From these data we conclude that a selective component of circulating γδ T cells traffics through the CNS. Thus, all major populations of lymphocytes can be detected in the normal CNS and as such may play specific roles in the immunological surveillance of that organ.