Immunology/Pathology Of Murine Leukemia Virus Infections

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Abstract

Significant new advances were made in discovering mechanisms by which regulatory T cells suppressed anti-viral CD8+ T cell responses in mice chronically infected with Friend retrovirus. Experiments revealed defects in CD8+ T cells in secretion of gamma interferon, perforin, granzyme A and granzyme B. Interestingly, much of the suppression of these proteins was at a post-transcriptional level. Immunotherapy using monoclonal antibodies to reverse suppression were partially successful in restoring anti-tumor CD8+ T cell responses in chronically infected mice. Significant progress was also made in establishing a cell culture system to study regulatory T cell suppression of CD8+ T cells. Virtually all aspects of in vivo responses have now been reproduced in vitro and this system will enable us to directly study intereactions between purified subsets of T cells. Our new information is leading to new avenues for modulating interactions between these critical components of antiviral immunity leading to treatments for chronic retroviral infections. Recent reports indicate that regulatory T cell suppression of CD8+ T cell responses is also occurring in HIV infections in humans and the degree of suppression correlates with viral loads. Thus our mouse model is extremely relvant to human retroviral infections and may lead to new therapies to treat chronic HIV infections.