Marrow-derived CD40-positive cells are required for mice to clear Cryptosporidium parvum infection

To clear a Cryptosporidium parvum infection, mice need CD4(+) T cells, majo r histocompatibility complex class II, and an intact CD40-CD154 signaling p athway. CD40 is constitutively expressed on marrow-derived cells such as de ndritic cells and B lymphocytes and is induced by gamma interferon (IFN-gam ma) on most somatic cells. To determine whether the CD40 needed to clear a C. parvum infection has to be on marrow-derived mononuclear cells or on the epithelial cells that normally harbor the parasite, we transplanted CD40(- /-) mice with CD40(+/-) bone marrow and then infected them with C. parvum, These chimeras cleared the C. parvum infection, while CD40(+/-) controls tr ansplanted with CD40(-/-) marrow cells remained infected. CD40 expression o n marrow-derived cells therefore suffices for a C. parvum infection to be c leared, while CD40 expression on intestinal epithelial cells is not suffici ent. There was no difference between the acquisition of CD69 and CD154 by m esenteric lymph node T cells of C. parvum-infected animals with intact or d isrupted CD40-CD154 pathways. CD4 T cells entered the intestinal laminae pr opriae of C. parvum-infected animals whether or not the CD40 genes of these recipients were intact. These results suggest that, for a C. parvum infect ion to be cleared, CD40 is not necessary for T-cell activation but may inst ead contribute to an effector pathway of marrow-derived cells.