Leishmania donovani infection of a susceptible host results in apoptosis of Th1-like cells: Rescue of anti-leishmanial CMI by providing Th1-specific bystander costimulation

A protective immune response against Leishmania donovani infection is media ted by T-helper type 1 (Th1) cells. Th1 induced cell-mediated immunity (CMI ), as assessed by anti-leishmanial DTH response, is lost in a susceptible h ost such as BALB/c mice. Although the impaired Th1 function eventuates in u nhindered parasite growth and in manifestation of the susceptible phenotype , the mechanism of down-regulation of the Th1 function is yet to be elucida ted. Here, we provide evidence that the parasite down-regulates the express ion of a Th1-specific costimulatory molecule, M150, on the surface of infec ted BALB/c mice-derived macrophages, Th cells are rendered unresponsive to anti-CD3 Ab-mediated stimulation after interaction with infected macrophage s. The anergized T cells produce much less IL-2, IL-4 and IFN-gamma compare d to those T cells which were costimulated using normal macrophages. The de fect in proliferation, anti-CD3 Ab induced unresponsiveness and IFN-gamma b ut not IL-4 production can be restored by providing bystander costimulation through M150, These results not only unfold a novel immune evasion strateg y used by the parasite but also clarify the mechanism of Th1 cell debilitat ion during the disease. Recovery of Th1 cytokine production by bystander co stimulation through M150 may help in formulating a new strategy for the eli mination of intracellular parasites.