The role of microglia and tumor-primed lymphocytes in the interaction between T lymphocytes and brain endothelial cells.
We investigated the role of IFN-gamma activated microglia in the passage of T lymphocytes across a monolayer of brain endothelial cells (EC) in vitro. Microglia isolated from Fisher 344 (F344) newborn rats were stimulated with IFN-gamma (100 U/ml) for 48 h. T lymphocytes primed with glioma cells were 51Cr-labeled, and added to the monolayer of F344 brain EC. In the adhesion assay, when EC were cultured in medium containing the supernatant of reactive microglia before the assay was carried out, the number of T lymphocytes adhering was increased. In addition, this adhesion was blocked by the addition of anti-ICAM-1 mAb to the EC. In the migration assay, performed using the double chamber system, when reactive microglia adhered to the other side of EC, the number of T lymphocytes migrating to the underwell was also increased. When T lymphocytes were primed to tumor cells in vivo, both their adhesion and migration were enhanced. These results suggest that some soluble factors from reactive microglia are capable of enhancing the expression of ICAM-1 on the brain EC. As a consequence, large numbers of tumor-primed T lymphocytes can adhere to EC and migrate across the EC monolayer.
Watanabe
T
T
Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata City, Japan. GBG00662@niftyserve.or.jp
Tanaka
R
R
Taniguchi
Y
Y
Yamamoto
K
K
Ono
K
K
Yoshida
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D003602:Cytotoxicity, Immunologic; D004730:Endothelium, Vascular / Q000166:cytology*; D018316:Gliosarcoma / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D007371:Interferon-gamma / Q000494:pharmacology; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D009368:Neoplasm Transplantation; D051381:Rats; D011916:Rats, Inbred F344; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000911:Antibodies, Monoclonal; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma