Vascular cell adhesion molecule 1 and α4 and β1 integrins in lymphocyte aggregates in Sjogren's syndrome and rheumatoid arthritis

Abstract

Objectives: Interactions between vascular cell adhesion molecule 1 (VCAM-1) and its ligand, the α4/β1 integrin, have been shown to be important in a number of cellular events in vitro. To assess the importance of such interactions in the development of lymphocytic infiltration in diseased tissue the distribution of the two ligands has been studied immunohistochemically. Methods: Cryostat sections of labial tissue from patients with Sjogren's syndrome, normal labial tissues, rheumatoid synovia, and normal tonsils were stained using antibodies to VCAM-1, α4 and β1 integrin chains, and markers for T cells, B cells, macrophages, and follicular dendritic reticulum cells (FDRCs), visualised using alkaline phosphatase and fast red. Results: Staining patterns for VCAM-1 and integrin chains in lymphocyte aggregates in synovial and labial tissues were similar. VCAM-1 staining was found on both vascular and ramifying dendritic cells at the centre of large T cell aggregates and in all aggregates where there was a central clustering of B cells. VCAM-1 colocalised with, but also extended beyond, staining for the FDRC marker R4/23. Staining for the α4 and β1 integrin chains was more widespread than staining for VCAM-1, with no significant increase in staining at sites of maximum VCAM-1 staining. In tonsils VCAM-1 and R4/23 codistributed in germinal centres, but staining for the α4 and β1 integrin chains was chiefly seen in T lymphocyte areas. Conclusions: VCAM-1 may be more important in determining the distribution of B than T lymphocytes in lymphocytic infiltration of non-lymphoid tissue. Unlike the follicles of lymphoid tissue, ectopic follicle-like structures in non-lymphoid tissues may form by immigration of B cells via VCAM-1+ vessels at the centre of T cell aggregates.