Antigen-specific damage to brain vascular endothelial cells mediated by encephalitogenic and nonencephalitogenic CD4+ T cell lines in vitro.
Experimentally induced and naturally occurring inflammatory diseases of the central nervous system (CNS) are often associated with a breakdown of the blood-brain barrier and edema within the CNS itself. CD4+ T cells are now clearly implicated in the pathogenesis of the induced CNS disease, experimental autoimmune encephalomyelitis, and previous in vivo experiments had indicated that these cells may be capable of directly damaging the CNS vasculature. To assess the capacity of CD4+ T cells to damage brain vascular endothelial cells (EC) in vitro, two lines with specificity for myelin basic protein and OVA were prepared and added to cultures of EC. We show here that both lines, when added in a resting state, severely disrupt the EC monolayers in an Ag-specific manner. The interaction is dependent on the recognition of Ag in the context of MHC class II and is blocked in the presence of mAb specific for CD4. Addition of T cell lines preactivated on irradiated thymocyte APC caused a high level of Ag nonspecific damage to the EC, which was not blocked by the addition of anti-CD4 mAb. Supernatants derived from these latter cells did not alone damage the EC monolayers despite the presence of TNF activity suggesting that T cell-EC contact may be required for these cell lines to mediate their effector function. Both resting and preactivated lines adhered strongly to the EC in the absence of Ag. The capacity of CD4+ T cells to strongly adhere to, and disrupt the integrity of, brain vascular EC may be important in the early stages of CNS disease mediated by this cell type.
Sedgwick
J D
JD
MRC Cellular Immunology Unit, Sir William Dunn School of Pathology, University of Oxford, U.K.
Hughes
C C
CC
Male
D K
DK
MacPhee
I A
IA
ter Meulen
V
V
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001921:Brain / Q000098:blood supply* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D004730:Endothelium, Vascular / Q000276:immunology*; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D004676:Myelin Basic Protein / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D004676:Myelin Basic Protein; D014409:Tumor Necrosis Factor-alpha; D010047:Ovalbumin