First Author | Ferlin WG | Year | 1998 |
Journal | Eur J Immunol | Volume | 28 |
Issue | 2 | Pages | 525-31 |
PubMed ID | 9521062 | Mgi Jnum | J:46693 |
Mgi Id | MGI:1201842 | Doi | 10.1002/(SICI)1521-4141(199802)28:02<525::AID-IMMU525>3.0.CO;2-M |
Citation | Ferlin WG, et al. (1998) The induction of a protective response in Leishmania major-infected BALB/c mice with anti-CD40 mAb. Eur J Immunol 28(2):525-31 |
abstractText | 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. |