The induction of a protective response in Leishmania major‐infected BALB/c mice with anti‐CD40 mAb

• Published in: European journal of immunology Vol. 28; no. 2; pp. 525 - 531
• Main Authors: Ferlin, Walter G., von der Weid, Thierry, Cottrez, Françoise, Ferrick, David A., Coffman, Robert L., Howard, Maureen C.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag GmbH 01-02-1998
• Subjects: AIDS/HIV; Animals; Antibodies, Monoclonal - therapeutic use; CD40; CD40 Antigens - immunology; Cytokine; Cytokines - biosynthesis; Female; Immunity, Innate; Leishmania major; Leishmania major - immunology; Leishmaniasis, Cutaneous - genetics; Leishmaniasis, Cutaneous - immunology; Leishmaniasis, Cutaneous - prevention & control; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; T-Lymphocytes - immunology; Th1 Cells - metabolism; Th1/Th2
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/(SICI)1521-4141(199802)28:02<525::AID-IMMU525>3.0.CO;2-M

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 × 129 mice that were rendered T cell deficient (TCR β–/– × TCR δ–/–) and L. major susceptible. Anti‐CD40 mAb stimulation of L. major‐infected BALB/c mice was accompanied by increased IL‐12 and IFN‐γ production in draining lymphnodes, 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‐γ 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. majorinfection and raises the possibility of utilizing this approach for vaccination strategies.