TABLE 1.

Nonrheumatic diseases in which CD40-CD40L interactions may play a role

Disease	Explanation
AIDS	CD40L is necessary for immune defense against human immunodeficiency virus and opportunistic infections (31, 32); this may overlie the similarity of clinical manifestations of AIDS to those of the congenital CD40L deficiency (hyper IgM syndrome)
Cancer	Efforts are being made to enhance antitumor immunity; an orally administered CD40L gene therapy has been tried recently against lymphoma (34)
Chronic lymphocytic leukemia	Malignant cells express both CD40 and CD40L, and their interaction may contribute to tumor growth, making CD40L a therapeutic candidate target (51)
Hodgkin's disease	The CD40L survival pathway is augmented in patients with B-cell malignancies (9)
Pulmonary fibrosis	CD40-CD40L interaction mediates fibroblast activation and production of the profibrotic cytokine transforming growth factor β (55); human lung fibroblasts from normal and scarred lung express CD40L; this expression is augmented by the profibrotic cytokine IL-13 and is downregulated by gamma interferon, a cytokine with antiscarring properties; fibroblast cell lines from human idiopathic pulmonary fibrosis tissue express high levels of CD40L compared to fibroblasts from nonscarred lungs (30)
Alzheimer's disease	CD40-CD40L is a critical enhancer of microglial cell activation (60)