1/3. Fatal adult case of severe lymphocytopenia associated with reactivation of human herpesvirus 6.It has been suggested that immunosuppression associated with human herpesvirus 6 (HHV-6) infection is a result of functional impairment or direct destruction of immunological cells. The ability of the virus to infect and destroy lymphocytes may cause progressive immunodeficiency in an infant with primary HHV-6 infection. An adult patient is described who had a fatal cytomegalovirus (CMV) infection due to severe and prolonged lymphocyte depletion associated with HHV-6 reactivation. The HHV-6 antibody titers were increased significantly after reactivation, and the virus was isolated from his peripheral blood mononuclear cells. The quantity of both HHV-6 and CMV dna was determined by using real-time PCR in plasma samples collected serially. HHV-6 DNAemia persisted for 1 month, which started just 1 week after the onset of lymphocytopenia. In contrast to HHV-6, CMV DNAemia was detected in the terminal phase of the illness. Thus, HHV-6 reactivation may have been the cause of the severe lymphocyte depletion and fatal CMV infection.- - - - - - - - - - ranking = 1keywords = herpesvirus (Clic here for more details about this article) |
2/3. Familial NK cell deficiency associated with impaired IL-2- and IL-15-dependent survival of lymphocytes.We previously reported the clinical phenotype of two siblings with a novel inherited developmental and immunodeficiency syndrome consisting of severe intrauterine growth retardation and the impaired development of specific lymphoid lineages, including transient CD8 alphabeta T lymphopenia and a persistent lack of blood NK cells. We describe here the elucidation of a plausible underlying pathogenic mechanism, with a cellular phenotype of impaired survival of both fresh and herpesvirus saimiri-transformed T cells, in the surviving child. Clearly, NK cells could not be studied. However, peripheral blood T lymphocytes displayed excessive apoptosis ex vivo. Moreover, the survival rates of CD4 and CD8 alphabeta T cell blasts generated in vitro, and herpesvirus saimiri-transformed T cells cultured in vitro, were low, but not nil, following treatment with IL-2 and IL-15. In contrast, Fas-mediated activation-induced cell death was not enhanced, indicating a selective excess of cytokine deprivation-mediated apoptosis. In keeping with the known roles of IL-2 and IL-15 in the development of NK and CD8 T cells in the mouse model, these data suggest that an impaired, but not abolished, survival response to IL-2 and IL-15 accounts for the persistent lack of NK cells and the transient CD8 alphabeta T lymphopenia documented in vivo. Impaired cytokine-mediated lymphocyte survival is likely to be the pathogenic mechanism underlying this novel form of inherited and selective NK deficiency in humans.- - - - - - - - - - ranking = 0.4keywords = herpesvirus (Clic here for more details about this article) |
3/3. Progressive immunodeficiency and fatal pneumonitis associated with human herpesvirus 6 infection in an infant.Human herpesvirus 6 (HHV-6), an important opportunistic pathogen in immunocompromised patients, causes fatal pneumonitis, encephalitis, and bone marrow suppression. Its ability to infect and destroy T lymphocytes may allow it to synergize with the human immunodeficiency virus in the destruction of lymphoid tissues in patients with AIDS. We describe herein an infant who had an immunodeficiency associated with thymic atrophy and severe T lymphocytopenia who developed fatal pneumonitis due to HHV-6. Dense and disseminated infection of T lymphocytes with HHV-6 was also documented. In the absence of any other documented cause of immunodeficiency, we hypothesize that congenital infection of this infant with HHV-6 may have caused progressive destruction of her cellular immune system, leading to the fatal pneumonitis. Thus, HHV-6 infection may have been the cause of both her immunodeficiency and her fatal opportunistic infection.- - - - - - - - - - ranking = 1keywords = herpesvirus (Clic here for more details about this article) |