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, major histocompatibility complex class II, and an intact CD40-CD154 signaling pathway. CD40 is constitutively expressed on marrow-derived cells such as dendritic cells and B lymphocytes and is induced by gamma interferon (IFN-gamma) 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 transplanted with CD40-/- marrow cells remained infected. CD40 expression on marrow-derived cells therefore suffices for a C. parvum infection to be cleared, while CD40 expression on intestinal epithelial cells is not sufficient. There was no difference between the acquisition of CD69 and CD154 by mesenteric lymph node T cells of C. parvum-infected animals with intact or disrupted CD40-CD154 pathways. CD4 T cells entered the intestinal laminae propriae of C. parvum-infected animals whether or not the CD40 genes of these recipients were intact. These results suggest that, for a C. parvum infection to be cleared, CD40 is not necessary for T-cell activation but may instead contribute to an effector pathway of marrow-derived cells.
Hayward
A R
AR
Department of Pediatrics and the Barbara Davis Childhood Diabetes Center, University of Colorado School of Medicine, Denver, Colorado, USA. anthony.hayward@uchsc.edu
Cosyns
M
M
Jones
M
M
Ponnuraj
E M
EM
D019264:Adoptive Transfer; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology*; D016026:Bone Marrow Transplantation; D019013:CD40 Antigens / Q000235:genetics / Q000276:immunology*; D003457:Cryptosporidiosis / Q000276:immunology*; D016785:Cryptosporidium parvum / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016513:Mice, SCID; D011828:Radiation Chimera; D013601:T-Lymphocytes / Q000276:immunology
D019013:CD40 Antigens