EXPRESSION OF COSTIMULATORY MOLECULES B7-1 AND B7-2 IN MACROPHAGES AND GRANULOMAS OF CROHNS-DISEASE - DEMONSTRATION OF CELL-TO-CELL CONTACTWITH T-LYMPHOCYTES

The pathogenesis of Crohn's disease, an intractable inflammatory disea se, involves impaired and/or excessive activation of mucosal macrophag es and T lymphocytes. B7-1 (CD80) and B7-2 (CD86) molecules are costim ulatory molecules that are indispensable to T-cell activation by antig en-presenting cells. To elucidate the roles and characteristics of the se antigen-presenting cells in Crohn's disease, in situ localization o f B7-1 and B7-2 (in relation to the distribution of T cells) was clari fied by light and electron microscopic immunohistochemistry. The resul ts were compared with those from a study of ulcerative colitis. Normal colonic tissue expressed B7-1 or B7-2 only sporadically. In active Cr ohn's disease, however, an increase in the number of B7-1/B7-2(+) cell s correlated with an increase in expression of HLA-DR and intercellula r adhesion molecule-1. Most B7-1/B7-2(+) cells were identified as nonc aseating granulomas or as macrophages, which tended to form an aggrega te especially in ulcer bases. In active ulcerative colitis, the increa se of B7-1/B7-2(+) cells was not as prominent as that in Crohn's disea se. Double immunohistochemistry revealed a close cellular distribution between noncaseating granulomas and T cells. Immunoelectron microscop y confirmed the expression of B7-1/B7-2 along the plasma membranes of cytoplasmic processes of granuloma cells, where lymphocytes were close ly attached. The present study suggested that granuloma formation in C rohn's disease is coupled with antigen presentation via a B7-1/B7-2-CD 28 pathway, which may contribute to the pathogenesis of the disease.