LRG-47, an IFN-gamma inducible 47kDa GTP binding protein was shown to play a major role in acute resistance to Mycobacterium avium infection, mice deficient in this molecule displaying even higher bacterial loads initially than IFN-gamma receptor knock-out animals. While the infected LRG-47 deficient animals developed normal numbers of IFN-gamma producing T cells, the granulomas that formed in these animals failed to show the lymphocyte infitration normally seen in wild-type granulomas. These findings suggest that while not effecting T cell priming, LRG-47 controls an important function associated with lymphocyte recruitment and containment of mycobacteria within granulomas. In a related collaborative study monocytes from different blood donors were shown to vary in their ability to control the growth of Mycobacterium tuberculosis (MTb) following ATP treatment. This differential microbicidal activity was shown to be correllated with the individual's reactivity to PPD as measured by lymphocyte proliferation, those individuals with the strongest monocyte mediated killing showing the lowest PPD responses. The latter finding suggests that intrinsic differences in monocyte control of MTb maybe an important factor determining the outcome of bacterial exposure as assessed by PPD reactivity. In continuing studies on inflammatory bowel disease (IBD) induced by Helicobacter hepticus in an IL-10 deficient setting, we showed that the CD4 T cells which block bacterial induced disease in normal hosts appear to be distinct from conventional Th2 cells in their lack of dependence on IL-4. Also in contrast to T regulatory cells described in other models of IBD their suppressive activity requires IL-10 not TGF-beta.
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