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...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 1996-03, Vol.4 (3), p.283-289
Main Authors: Campbell, Kim A, Ovendale, Pamela J, Kennedy, Mary K, Fanslow, William C, Reed, Steven G, Maliszewski, Charles R
Format: Article
Language:English
Subjects:
AIDS/HIV
Animals
CD40 Antigens - physiology
CD40 Ligand
Disease Susceptibility
Immunity, Cellular
Interleukin-12 - biosynthesis
Interleukin-12 - genetics
Interleukin-12 - therapeutic use
Leishmania major
Leishmania major - immunology
Leishmaniasis, Cutaneous - genetics
Leishmaniasis, Cutaneous - immunology
Leishmaniasis, Cutaneous - prevention & control
Ligands
Macrophages, Peritoneal - metabolism
Membrane Glycoproteins - physiology
Membrane Glycoproteins - therapeutic use
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Recombinant Proteins - therapeutic use
Th1 Cells - immunology
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Summary: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.
ISSN:1074-7613
1097-4180
DOI:10.1016/S1074-7613(00)80436-7