BLOCKADE OF CD86 AMELIORATES LEISHMANIA-MAJOR INFECTION BY DOWN-REGULATING THE TH2 RESPONSE

The costimulatory molecules CD80 and CD86 affect the differentiation o f Th1 and Th2 subsets in experimental allergic encephalomyelitis, an a utoimmune disorder. It is reported that the CD86 costimulator signific antly affects disease outcome in Leishmania major infection, a classic model of Th subset polarization. Treatment of both L. major-resistant (C57BL/6) and susceptible (BALB/c) strains of mice with anti-CD86 sub stantially decreased parasite burden. This was accompanied, in BALB/c mice, by a decrease in Th2 cytokines. In contrast, anti-CD80 treatment did not affect parasite burden or cytokine levels in either strain. T hese data illustrate that in L. major infection, anti-CD86 can abrogat e Th2 differentiation in a Th2-dominated susceptible mouse and can ame liorate disease in a Th1-dominated resistant strain, although the mech anism involved in the latter is not clear. It is concluded that in L. major infection, Th2 subset differentiation is critically dependent on interaction with the CD86 costimulatory molecule.