Down‐regulation of microglia and NG2‐positive cells reaction in trimethyltin‐injured hippocampus of rats treated with myelin basic protein‐reactive T cells: Possible contribution to the neuroprotective effect of T cells

In our previous investigations, we demonstrated that CD4+ antimyelin basic protein (MBP) T cells protect hippocampal neurons against trimethyltin-induced damage. We hypothesized involvement of T cells, interacting with the various glial populations activated during the neurodegeneration process. In this study, we employ immunocytochemical methods to investigate the influence of administration of T cells on the response of microglia and of NG2+ cells to trimethyltin (TMT)-induced damage. Female Lewis rats were treated with anti-MBP CD4+ T cells (4 million per animal, i.v) 24 hr after TMT (8 mg/kg, i.p) intoxication. TMT caused degeneration of CA4 hipppocampal neurons and evoked an abundant reaction of microglial and NG2+ cells in the injured region. The cells changed morphology into the activated state, and the number of OX42+ and NG2+ cells increased about 4.5-fold and 3-fold, respectively, relative to controls as assessed on day 21 after TMT treatment. Additionally, the cells of ameboid morphology, which expressed NG2 or microglial antigens, appeared in the zone of neurodegeneration. Furthermore, certain cells of ameboid phenotype shared both antigens. In rats treated with T cells, down-regulation of the activation of both glial classes and reduction of formation of their ameboid forms was observed. The number of the total OX42+ and NG2+ cells decreased by 21% and 54%, respectively, and the number of their ameboid forms decreased by 46% and 73%, respectively. Our data suggest that the diminished activation of microglia and NG2+ cells, particularly the reduced number of their ameboid forms, may contribute to the neuroprotective effect of T cells. © 2009 Wiley-Liss, Inc.