THE ROLE OF VCAM-1/VLA-4 IN THE ACTIVATION OF ALLOGENIC T CELLS BY MURINE MACROPHAGES*

Vascular cell adhesion molecule 1 (VCAM-1) is a member of immunoglobnlin superfamily. The principal Hgand for VCAM-1 is integrin α4β1/VLA-4 (very late antigen 4). It was reported that VCAM-1 was expressed on macrophages and dendritic cells, hut little is known about its function on these professional antigen presenting cells (APe). The present study was performed to investigate the expression of VCAM-1 on macrophages and the role of VCAM-1/VLA-4 in the activation of allogeuic T ceils by murine macrophages. We analyzed VCAM-1 expression on peritoneal macrophages and macrophage cell line J774A.1 by fluorescence-activated cell sorting (FACS). Using neutralizing antibodies, we further analyzed the role of VCAM-1/VLA-4 interaction in macrophage and allogenic T cell mixed lymphocyte reaction (MLR). We found that VCAM-1 was constitutively expressed on macrophages and its expression level was upregnlated by soluble tumor associated antigen (freeze-thaw lysates of FBL-3 leukemia cells) and TNF-α. In MLR assays, we observed that blocking VCAM- 1/VLA-4 interaction with anti-VCAM-I or anti-VLA-4 mAbs caused significant inhibition of the proliferative response and IL-2 production. These results suggest that VCAM-1 on macrophages not only facilitates the cell-tocell contact through adhesive interaction but also plays a role in the costimulation of T cells via its interaction with VLA-4 on the T cells.