Disruption of CD40-CD40 ligand interactions results in an enhanced susceptibility to Leishmania amazonensis infection

Immunity. 1996 Mar;4(3):263-73. doi: 10.1016/s1074-7613(00)80434-3.


To study the role of CD40 ligand (CD40L) in the host immune responses against intracellular pathogens, we infected CD40L knockout (CD40L-/-) mice with Leishmania amazonensis. Although wild-type mice were susceptible to infection and developed progressive ulcerative lesions, tissue parasite burdens in CD40L-/- mice were significantly higher. This heightened susceptibility to infection was associated with an impaired T cell and macrophage activation and altered inflammatory response, as reflected by low levels of IFN gamma, lymphotoxin-tumor necrosis factor (LT-TNF), and nitric oxide (NO) production. Furthermore, CD40L-/- mice failed to generate a protective immune response after immunization. These results indicate an essential role of cognate CD40-CD40L interactions in the generation of cellular immune responses against an intracellular parasite.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Protozoan / biosynthesis
  • Antigens, Protozoan / immunology
  • CD40 Antigens / metabolism*
  • CD40 Ligand
  • Disease Susceptibility
  • Host-Parasite Interactions
  • Leishmania mexicana / immunology*
  • Leishmaniasis, Cutaneous / immunology*
  • Leishmaniasis, Cutaneous / pathology
  • Ligands
  • Macrophages, Peritoneal / metabolism
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Mutant Strains
  • Nitric Oxide / biosynthesis


  • Antibodies, Protozoan
  • Antigens, Protozoan
  • CD40 Antigens
  • Ligands
  • Membrane Glycoproteins
  • CD40 Ligand
  • Nitric Oxide