Robert D. Stout¹ and Jill Suttles²

Program in Immunology, Departments of Microbiology¹ and Biochemistry², James H. Quillen College of Medicine at East Tennessee State University, Johnson City, TN, USA

Received 4/15/97; Accepted 4/18/97; On-line 5/1/97

7. PERSPECTIVE

The studies on experimenal allergic encephalomyelitis to date strongly support critical roles for CD40 and TNF-alpha (CD40-induced?) in the pathogenesis of sclerotic lesions and for TGF-beta in remission of the inflammatory episode. Although receptors other than CD40 (e.g., CD23 and CD69) have been shown to stimulate macrophage production of inflammatory cytokines in vitro, their role in the pathogenesis of inflammatory disease is still unexplored. The studies on T cell receptor transgenic and CD40L-deficient mice (105) indicate that CD40-independent receptor:ligand pairs and/or cytokines are sufficient to drive the development of disease once the T cells are activated. This is supported by the observation that administration of anti-CD40L antibodies after immunization with encephalitogenic peptide only partially interferes with the development of disease. The identification of these CD40-independent receptors and of their role in the pathogenesis of inflammatory disease will be a major area of research interest throughout the next decade.