| First Author | Murray HW | Year | 2003 |
| Journal | Infect Immun | Volume | 71 |
| Issue | 11 | Pages | 6453-62 |
| PubMed ID | 14573667 | Mgi Jnum | J:86275 |
| Mgi Id | MGI:2679183 | Doi | 10.1128/IAI.71.11.6453-6462.2003 |
| Citation | Murray HW, et al. (2003) Modulation of T-cell costimulation as immunotherapy or immunochemotherapy in experimental visceral leishmaniasis. Infect Immun 71(11):6453-62 |
| abstractText | CD40 ligand (CD40L)-deficient C57BL/6 mice failed to control intracellular Leishmania donovani visceral infection, indicating that acquired resistance involves CD40-CD40L signaling and costimulation. Conversely, in wild-type C57BL/6 and BALB/c mice with established visceral infection, injection of agonist anti-CD40 monoclonal antibody (MAb) induced killing of approximately 60% of parasites within liver macrophages, stimulated gamma interferon (IFN-gamma) secretion, and enhanced mononuclear cell recruitment and tissue granuloma formation. Comparable parasite killing was also induced by MAb blockade (inhibition) of cytotoxic T lymphocyte antigen-4 (CTLA-4) which downregulates separate CD28-B7 T-cell costimulation. Optimal killing triggered by both anti-CD40 and anti-CTLA-4 required endogenous IFN-gamma and involved interleukin 12. CD40L(-/-) mice also failed to respond to antileishmanial chemotherapy (antimony), while in normal animals, anti-CD40 and anti-CTLA-4 synergistically enhanced antimony-associated killing. CD40L-CD40 signaling regulates outcome and response to treatment of experimental visceral leishmaniasis, and MAb targeting of T-cell costimulatory pathways (CD40L-CD40 and CD28-B7) yields macrophage activation and immunotherapeutic and immunochemotherapeutic activity. |
