Immune T cells from Mice Immunocompromised by Flt3 Ligand Treatment Confer a Greater Degree of Immunity to Recipient Mice Rechallenged with Listeria monocytogenes
Treatment of mice with human Flt3 ligand (FL) increases both lymphoid and myeloid dendritic cells (DC) in vivo. DC are the most potent professional antigen presenting cells for stimulating T-cells. Several studies have shown that FL treatment in vivo increases DC and enhances cell-mediated immunity. The most promising studies have shown FL induces complete tumor regression in mice. Resistance to infection with the intracellular pathogens Mycobacterium tuberculosis and Listeria monocytogenes (LM) is also mediated by cellular immunity. However, our lab has found that mice treated with FL and infected with either of the two pathogens had an impaired immune response indicated by higher organ bacterial numbers compared to controls. To assess the mechanism of these results, we hypothesized that amplified numbers of DC act as reservoirs for infection. To test this, varying numbers of DC from FL treated mice will be injected into naove mice prior to infection with LM. Bacterial numbers in both liver and spleen will be determined 3 and 8 days later. We will further test DC from FL treated mice by comparing their ability versus macrophages to kill LM and to present antigens for T-cell stimulation. We also hypothesized that T-cells from FL treated mice are not functional and unlike control T-cells will not confer immunity when transferred to naove recipients. To test this, we will infuse naove recipients with T-cells from donor mice treated with FL and LM infected. Recipients will then be infected and their immune responses evaluated by organ bacterial numbers.
