The induction of a protective response in Leishmania major-infected BALB/c mice with anti-CD40 mAb.
A protective immune response to the intracellular parasite Leishmania major requires the development of a Th1 CD4+ T cell phenotype. We demonstrate herein that BALB/c mice, which normally develop a susceptible Th2 response to L. major infection, are protected when co-injected with an agonistic anti-murine CD40 mAb. Anti-CD40 mAb-mediated protection in this system was found to be T cell dependent, since it was not observed in C57BL/6 x 129 mice that were rendered T cell deficient (TCR beta-/- x TCR delta-/-) and L. major susceptible. Anti-CD40 mAb stimulation of L. major-infected BALB/c mice was accompanied by increased IL-12 and IFN-gamma production in draining lymph nodes, analyzed either by direct expression, or in an antigen-specific in vitro recall assay. The protective role of these cytokines was indicated by the finding that anti-CD40 mAb-mediated protection of L. major-infected BALB/c mice could be reversed by co-treating the animals with neutralizing anti-IL-12 and/or anti-IFN-gamma mAb. Collectively, these data suggest that BALB/c mice develop a protective Th1 CD4+ T cell response to L. major infection when co-injected with anti-CD40 mAb. While the CD40-CD40L interaction has been previously shown to be vital in the control of murine Leishmaniasis, the current study establishes in vivo that anti-CD40 mAb treatment alone is sufficient to protect BALB/c mice from L. major infection and raises the possibility of utilizing this approach for vaccination strategies.
Ferlin
W G
WG
Department of Immunobiology, DNAX Research Institute, Palo Alto, CA, USA.
von der Weid
T
T
Cottrez
F
F
Ferrick
D A
DA
Coffman
R L
RL
Howard
M C
MC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D019013:CD40 Antigens / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D007113:Immunity, Innate; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000378:metabolism
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D016207:Cytokines