Cytotoxic cellular responses are crucial for clearing intracellular pathogens and generating host resistance. Experimental pulmonary tuberculosis is associated with an early delay in T cell responses and with elevated lung bacterial burden during chronic infection. In this study we quantified the in vivo cytotoxicity and the mycobacterial burden from two pertinent tissues in groups of mice infected each with a mycobacterial strain of different virulence. None of the strains induced cytotoxic responses during early (day 14) infection. Interestingly, at 21 and 60 days post-infection, Mycobacterium canettii (lowest virulence) triggered the strongest in vivo cytotoxicity both in lungs and mediastinal lymph nodes. In contrast, Mycobacterium tuberculosis H37Rv (intermediate virulence) and Beijing strains (highest virulence) induced lower cytotoxic responses, and exhibited high bacterial growth, especially in lungs. These in vivo data suggest that virulence of Mycobacterium strains are somehow associated with subverting cytotoxic responses, thus contributing to early bacterial replication and subsequent persistence in the lungs.
Murine dialyzable spleen extracts (DSE) are similar to Transfer Factors in that they can transfer cell mediated immunity (CMI) from an immunocompetent organism into a naïve one in an antigen-specific manner. Lymphoid organs from rats treated with transfer factor have shown histological changes and increased lymphoblasts and plasmocytes. In this work we investigated if treating mice with DSE obtained from OVA immunized mice (DSEova) could modify the humoral immune response against OVA in naïve mice. Methods. DSEova preparation: splenic cell suspensions from OVA immunized BALB/c mice were disrupted by freeze-thaw cycles, extracts were then dialyzed with a membrane pore of 10 kDa. BALB/c mice were treated with 20μg of DSEova alone. Serum samples were obtained between days 0-36, and IgM and IgG anti-OVA were assayed by ELISA. Mice were sacrified on days 9, 15 and 23 post-immunization, and germinal centers (GC) in lymph nodes were identified by immunohistochemistry using PNA and THY-1. Results. Compared to control saline-treated animals, DSEova treated mice produced IgM and IgG anti-OVA. Compared to saline-treated mice, DSEova-mice showed increased numbers of GC, but of smaller size than OVA-treated mice. Conclusion. In this in-vivo model, compared to control-mice, DSEova would appear to stimulate the Ag-specific antibody responses and the appearance of GC.
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