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Cellular Immune Changes in the Peripheral Blood of Subjects Chronically Infected with XMRV
AuthorGoetz, Deborah L.S.
AdvisorWalker, Mark J.
Natural Resources and Environmental Science
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Retroviruses chronically alter the regulation of the innate immune system causing immunosuppression. Recently, evidence of a new human retrovirus, Xenotropic murine leukemia virus-related virus, XMRV, was detected in the blood of >67% of 101 Chronic Fatigue Syndrome (CFS) patients tested and shown to be infectious. CFS is a debilitating disease characterized by innate immune system activation and low natural killer (NK) cell activity. We hypothesized that XMRV infection plays a role in the pathogenesis of CFS through the dysregulation of the innate immune and/or the adaptive immune responses. We addressed this hypothesis by phenotypic analysis of leukocyte subsets by multiplex flow cytometry in CFS patients infected with XMRV versus uninfected controls. While there was no significant difference in total cellularity and CD45+ leukocytes between XMRV-infected CFS patients and XMRV negative controls, we found significant reductions in the percentage of CD45+ lymphocytes, CD45+ CD3- lymphocytes, CD45+ CD3- CD19- CD56+ NK cells and CD19+ B cells. Moreover, the NK phenotype in XMRV+ patients was altered, with 80% of XMRV+ patients having a significantly reduced CD56DIM population. Within this CD56DIM population present in XMRV+ patients, only 40% express CD16. XMRV infected patients showed a important increase in CD3+ CD56+ NKT cells with a NK to NKT ratio that was 55% higher than XMRV- healthy controls. The B cells present in the peripheral blood of XMRV+ CFS patients contained a remarkable CD20+, CD23+ mature B cells. The myeloid cell compartment showed an increased population of activated antigen presenting cells. These data suggest a chronic innate immune activation in XMRV-infected subjects which cause innate and adaptive immune deficiency, similar to those seen in other human retroviral infections. These data also suggest that the immunological defects seen in some CFS patients could be attributed to XMRV infection either directly though XMRV infection of specific leukocyte subsets or indirectly through the dysregulation of cytokines and chemokines.