DEFICIENT EXPRESSION OF COSTIMULATORY MOLECULES ON LEISHMANIA-INFECTED MACROPHAGES

Co-stimulatory signals are necessary for the full activation of T cell s for growth and effector function. As co-stimulatory molecules are no rmally regulated in their expression, it has been suggested that micro organisms enhance their expression on host antigen-presenting cells (A PC), thus allowing efficient generation of anti-microbial immunity. We here describe experiments which demonstrate that infection of macroph ages, both in vitro and in vivo, by the protozoan parasite Leishmania donovani fails to trigger expression of costimulatory molecules B7-1 a nd heat-stable antigen on these APC. Furthermore, infection with this parasite inhibits the macrophage response to normal regulatory signals , such as bacterial lipopolysaccharide. These changes in the cell surf ace are mirrored in functional studies of co-stimulation in vitro. Tog ether, these data suggest a further facet of parasite interference in host immunity, but also indicate a potential new target for immunother apy.