Immunology And Pathology Of Acute and Chronic Murine Leukemia Virus Infections

National Institute Of Allergy And Infectious Diseases

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Abstract

In FY2018 the Retroviral Immunology Section continued investigation into host mechanisms of genetic resistance and susceptibility to retroviral infection. These findings have implications for the design of therapeutics and vaccines to treat and prevent infections with viruses such as HIV. Previous studies of Friend retrovirus-infected mice revealed that B cells were absolutely required for the induction of regulatory T cell (Treg) responses during infection. In follow up studies we have now shown that the Tregs induced by B cells then go on to suppress both the antigen presentation and immunoglobulin production activities of the B cells. The suppressed antigen presentation functions had downstream effects on T cell responses as well. Thus, there is an intricate feedback loop of general immunoregulation involving B cells and Tregs during viral infection (Moore et al. mBio 10: e02578-18 2019). Further experiments studying immunity in the Friend virus model showed that natural or polyreactive antibodies are also under the immunosuppressive control of regulatory T cells. Results from mice deficient in regulatory T cells or depleted of regulatory T cells both indicated that natural antibody titers were significantly higher when regulatory T cell responses were dampened. We have now collected evidence that some human patients with Treg deficiencies also have strongly elevated levels of natural antibodies. Major advances have been made in examining the role of SIRP alpha in marking the functional subset of virus-specific CD8+ T cells present in chronically infected animals and humans. We have found that not all CD8+ T cells in chronic infections are exhausted and that residual functional cells express SIRP alpha, a molecule previously thought to be only expressed by myeloid cells, stem cells and neurons (Myers et al. Nature Comm. 10: 794 2019).