Evaluation of murine OX40L-murine IgG1(MM1) fusion protein on immunogenicity against L. mexicana infection in BALB/c mice.

The majority of OX40L is found on professional antigen-presenting cells (APC), the potency of OX40L to enhance the immunogenicity of potential vaccines against leishmania is not yet fully investigated. There is no report of administration of OX40L on cutaneous leishmaniasis either in therapy or prophylactic immunisation and the present study for the first time reports the effect of OX40L on L. mexicana infection. In this study, B9B8E2 cells were transfected with the murine OX40L and IgG1 plasmids, were used to produce the mOX40-mIgG1 (MM1). The therapeutic effects of MM1(mOX40L-mIgG1) was tested in a challenge experiment using L. mexicana infected BALB/c mice. Mice received two doses of MM1, on day 3 and 7 after the infection. Mice receiving MM1 generated an inflammatory reaction a few days after the injection of the OX40L, which was gradually dampened and finally disappeared 3 weeks later. There was a significant delay in the growth of developing lesions in mice receiving OX40L compared to controls injected with PBS and the size of lesions in the group receiving MM1 was significantly smaller than that of injected with either PBS. 40% of mice given MM1 remained lesion free for two months, when experiments were terminated. The results clearly indicate the high therapeutic effect of mOX40L-mIgG1 fusion protein in L. mexicana infection. The effect of OX40L on the enhancement of immunisation, needs to be further investigated for developing new vaccine strategies.

Inhibitory Effects of Leishmania Mexicana Infection on MHC-I Expression in Bone Marrow Derived Dendritic Cells.

Background: Leishmania is a parasite causing leishmaniasis with different clinical manifestations depending on the infectious species in many countries worldwide. Although different studies have been taken place to clear the interaction of the parasite with the immune system, many aspects of immunology of leishmaniasis is remained uncertain. Methods: Bone marrow derived dendritic cells (DCs) were cultured in vitro and divided into different groups (Nottingham Trent University, Nottingham, UK). The groups were separately infected with live or autoclaved L. mexicana or loaded with Soluble Leishmania Antigen (SLA). The expression of major histocompatibility complex class I (MHC-I) molecule was checked and compared on the cultured DCs using flow cytometry. Results: Infection of L. mexicana caused a significant downregulation in expression of molecules where killed Leishmania or SLA could not induce suppression in expression of these molecules. Conclusion: L. mexicana infection results in downregulation of MHC-I expression on bone marrow-derived dendritic cells.