The Role of VCAM-1/VLA-4 in the Activation of Allogenic T Cells by Murine Macrophages / 中国肿瘤生物治疗杂志

ABSTRACT

Vascular cell adhesion molecule 1 (VCAM - 1) is a member of immunoglobulin superfamily. The principal ligand for VCAM - 1 is integrin ?4|?1/VLA - 4(very late antigen 4). In recent years, VCAM - 1 was found to be expressed on macrophages and dendritic cells, but little is known about its identity on these professional antigen presenting cells (APC). In the present study we analyzed VCAM - 1 expression on macrophages by fluorescence - activated cell sorting (FACS) and found that VCAM- 1 was constitutively expressed on macrophages and its expression level was up-regulated by soluble tumor associated antigen (TAA freeze - thaw lysates of FBL - 3 tumor cells) and TNF - a. In macrophages and allogenic T cells mixed lymphocyte reaction (MLR) assays, we observed that blocking VCAM - 1/VLA - 4 interaction with anti - VCAM - 1 or anti - VLA - 4 mAbs caused significant inhibition of the proliferative response and inhibition of IL - 2 production. These findings suggest that VCAM - 1 on macrophages not only allows for increased cell-to-cell contact through adhesive interaction but also plays a role in the costimulation of T cells via its interaction with VLA-4.