Differential expression of costimulatory molecules B7-1 and B7-2 on microglial cells induced by Th1 and Th2 cells in organotypic brain tissue

Autoreactive T-cells are involved in demyelination, neurodegeneration, and the recruitment of peripheral macrophages and nonspecific activated T-cells in autoimmune diseases such as multiple sclerosis (MS). The ligation of co stimulatory B7 molecules on microglia with CD28/CTLA-4 on T-cells is though t to be crucial to the onset and course of MS and its rodent model experime ntal autoimmune encephalomyelitis (EAE). It is currently unclear as to how far the nature of infiltrating T-cells has an impact on the expression of t he B7 molecules on microglia, the resident antigen-presenting cells (APCs) of the brain. We studied the expression of B7-1 and B7-2 on microglia after encounter with preactivated Th1 and Th2 cells from transgenic mice whose T -cells express a receptor (TCR) either specific to myelin basic protein (MB P) or ovalbumin (OVA) using murine organotypic entorhinal-hippocampal slice cultures (OEHSC). Our main finding was that Th1 cells downregulate the con stitutive expression of B7-2 and induce B7-1 expression while Th2 cells do not induce this B7-1 upregulation. The main difference between MBP- and OVA -specific cells was seen in experiments were Th1 cells had direct contact t o APCs but not to brain tissue. In contrast to MBP-specific Th1 cells, OVA- specific Th1 cells required the addition of antigen to upregulate B7-1 and downregulate B7-2. When the cells were allowed to have contact to brain tis sue, no difference was seen in the pattern of B7 regulation between OVA- an d MBP-specific T-cells. Our data suggest that T-cells are able to modulate B7 expression on microglial cells in the brain independent of antigen prese ntation through TCR/MHC-II ligation but presumably by soluble mediators. (C ) 2001 Wiley-Liss, Inc.