Role of central nervous system microvascular pericytes in activation of antigen-primed splenic T-lymphocytes

The cellular constituents of the blood-brain barrier (BBB) must make finely tuned, regulatory responses to maintain microvascular homeostasis. The mec hanisms by which this task is accomplished are largely unknown. However, it is thought they involve a series of cross-talk mechanisms among endothelia l cells (EC), pericytes (PC), and astrocytes. During inflammation, the BBB is exposed to a number of biological response modifiers including cytokines released by infiltrating leukocytes, The response to inflammatory cytokine s may alter the normal regulatory function of EC and PC. These changes may account for some of the pathological findings in central nervous system (CN S) inflammatory disease. Previous studies have shown that PC and EC may hav e immune potential. We have investigated the response of the PC to a variet y of inflammatory cytokines, Primary rat PC constitutively express low leve ls of intercellular adhesion molecule-1 (ICAM-1) and major histocompatibili ty complex (MHC) class I molecule, which can be upregulated in response to the cytokine interferon-gamma (IFN gamma). IFN gamma also induced the expre ssion of MHC class II molecule. After induction of MHC class II molecule, C NS PC acquired the capacity to present antigen to primed syngeneic rat T-ly mphocytes. Antigen presentation by PC was comparable to that seen with clas sic antigen presenting cells. A small number of primary PC constitutively e xpress low levels of vascular cell adhesion molecule-1 (VCAM-1), which was increased on exposure to tumor necrosis factor-alpha. (TNF alpha). Results suggest that CNS PC respond to inflammatory cytokines, are involved in T-ly mphocyte activation, and express cell surface adhesion molecules (VCAM-1, I CAM-1) that may provide costimulatory activity, It is likeIy that CNS PC ar e important in neuroimmune networks at the BBB. (C) 1999 Wiley-Liss, Inc.