Protective role of CD40 in Leishmania major infection at two distinct phases of cell-mediated immunity

Immunity. 1996 Mar;4(3):275-81. doi: 10.1016/s1074-7613(00)80435-5.


CD40-deficient mice are susceptible to Leishmania major infection while their wild-type littermates can resolve the infection. Upon stimulation with L. major antigens, draining lymph node T cells of the mutant mice and the susceptible mice, BALB/c, secrete comparable amounts of IL-4. The mutant mice produce less IFN gamma than wild-type mice. The expression of IL-12 p40 mRNA was significantly lower in L. major antigen-stimulated cells of mutant mice than those of wild-type or BALB/c mice. In normal mice, engagement of CD40 activates macrophages to a leishmanicidal state in vitro in the presence of IFN gamma. The results suggest that the CD40-CD40 ligand interaction plays an important role in two critical steps of cell-mediated immunity to L. major infection: the generation of a Th1 response and activation of macrophages to a leishmanicidal state.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Protozoan / immunology
  • CD40 Antigens / genetics
  • CD40 Antigens / physiology*
  • Cells, Cultured
  • Disease Susceptibility
  • Epitopes / immunology
  • Immunity, Cellular
  • Interleukin-12 / biosynthesis
  • Interleukin-12 / genetics
  • Leishmania major / immunology*
  • Leishmaniasis, Cutaneous / genetics
  • Leishmaniasis, Cutaneous / immunology*
  • Leishmaniasis, Cutaneous / prevention & control
  • Macrophage Activation
  • Macrophages, Peritoneal / immunology
  • Macrophages, Peritoneal / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Mutant Strains
  • RNA, Messenger / biosynthesis
  • Th2 Cells / immunology
  • Th2 Cells / metabolism


  • Antigens, Protozoan
  • CD40 Antigens
  • Epitopes
  • RNA, Messenger
  • Interleukin-12