REQUIREMENT FOR CD40-CD40 LIGAND INTERACTION FOR ELIMINATION OF CRYPTOSPORIDIUM-PARVUM FROM MICE

Mice with disrupted genes for CD40 and CD40 ligand (CD40L) are unable to clear infection with Cryptosporidium parvum and develop cholangitis , Parasites are present in the gut, gall bladder, and biliary tree, an d biliary epithelial cells express CD40 on the cell surface, SCID mice infected with C. parvum for >1 month can clear the infection after re constitution with spleen cells from CD40, but not CD40L, knockout mice , In an in vitro model, C. parvum-infected HepG2 cells were triggered to apoptosis when incubated with a CD40L-CD8 fusion protein, The requi rement for CD40-CD40L interactions for immunity to C. parvum indicated by our results may entail the triggering of apoptosis in infected cel ls, in addition to the known role of CD40L-CD40 interactions in stimul ating cytokine production and promoting T-cell responses.