Protective role of CD40 in Leishmania major infection at two distinct phases of cell-mediated immunity.
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.
Kamanaka
M
M
Institute for Molecular and Cellular Biology, Research Institute for Microbial Diseases, Osaka University, Japan.
Yu
P
P
Yasui
T
T
Yoshida
K
K
Kawabe
T
T
Horii
T
T
Kishimoto
T
T
Kikutani
H
H
D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D019013:CD40 Antigens / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D004198:Disease Susceptibility; D000939:Epitopes / Q000276:immunology; D007111:Immunity, Cellular; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D012333:RNA, Messenger / Q000096:biosynthesis; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D000953:Antigens, Protozoan; D019013:CD40 Antigens; D000939:Epitopes; D012333:RNA, Messenger; D018664:Interleukin-12