CD40 ligand is required for protective cell-mediated immunity to Leishmania major.
The CD40-CD40 ligand (CD40L) signaling process is a pivotal component of multiple immunoregulatory pathways. Although the role that CD40L plays in humoral immune responses is fairly well defined, its function(s) in cell-mediated responses in vivo has not been established. We investigated this issue by assessing the course of Leishmania major infection in CD40L knockout (CD40LKO) mice that were generated on a resistant background. In response to parasite challenge, CD40LKO mice developed ulcerating cutaneous lesions and failed to mount a vigorous Th1-like response. The impaired Th1-like response appears to be related to a defect in the ability of CD40LKO T cells to induce the production of IL-12 from macrophages. Treatment with exogenous IL-12 prevented disease progression in CD40LKO mice, and administration of recombinant CD40L provided partial protection against infection. Thus, a protective cell-mediated immune response to L. major appears to be dependent upon CD40L-induced IL-12 secretion by antigen-presenting cells.
Campbell
K A
KA
Department of Cellular Immunology, Immunex Corporation, Seattle, Washington 98101, USA.
Ovendale
P J
PJ
Kennedy
M K
MK
Fanslow
W C
WC
Reed
S G
SG
Maliszewski
C R
CR
D000818:Animals; D019013:CD40 Antigens / Q000502:physiology*; D023201:CD40 Ligand; D004198:Disease Susceptibility; D007111:Immunity, Cellular; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D008024:Ligands; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000502:physiology* / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011994:Recombinant Proteins / Q000627:therapeutic use; D018417:Th1 Cells / Q000276:immunology
D019013:CD40 Antigens; D008024:Ligands; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D023201:CD40 Ligand; D018664:Interleukin-12