Immunotherapy with OX40L-Fc or anti-CTLA-4 enhances local tissue responses and killing of Leishmania donovani


Zubairi, S; Sanos, SL; Hill, S; Kaye, PM; (2004) Immunotherapy with OX40L-Fc or anti-CTLA-4 enhances local tissue responses and killing of Leishmania donovani. European journal of immunology, 34 (5). pp. 1433-40. ISSN 0014-2980 DOI: 10.1002/eji.200324021

Full text not available from this repository.

Abstract

Enhancing granuloma development and effector function, but without inducing the pathology associated with excess granulomatous inflammation, poses a major challenge for immunotherapeutic intervention against diseases such as visceral leishmaniasis (VL). Here, we demonstrate that a chimeric fusion protein (OX40L-Fc) which stimulates T cells through OX40 and a monoclonal antibody which blocks CTLA-4, an inhibitory receptor on T cells, both enhanced the rate of granuloma maturation, CD4(+) T cell proliferation, and killing of Leishmania. Costimulation-based therapy induced no adverse fibrotic or necrotic reactions, and had no significant effect on the levels of endogenous anti-inflammatory cytokines (IL-10 and TGF-beta). Furthermore, both OX40L-Fc and anti-CTLA4could be co-administered with conventional anti-leishmanial drugs. Until now, enhancing T cell immunity by the manipulation of costimulatory pathways has only received serious attention for cancer immunotherapy, but our data provide a compelling argument for the evaluation of this approach in human VL and other infectious diseases.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Research Centre: Leishmaniasis Group
PubMed ID: 15114677
Web of Science ID: 221427400022
URI: http://researchonline.lshtm.ac.uk/id/eprint/14768

Statistics


Download activity - last 12 months
Downloads since deposit
0Downloads
269Hits
Accesses by country - last 12 months
Accesses by referrer - last 12 months
Impact and interest
Additional statistics for this record are available via IRStats2

Actions (login required)

Edit Item Edit Item