title: Antigen-dependent and -independent mechanisms of T and B cell hyperactivation during chronic HIV-1 infection.
abstract: Continuous loss of CD4(+) T lymphocytes and systemic immune activation are hallmarks of untreated chronic HIV-1 infection. Chronic immune activation during HIV-1 infection is characterized by increased expression of activation markers on T cells, elevated levels of proinflammatory cytokines, and B cell hyperactivation together with hypergammaglobulinemia. Importantly, hyperactivation of T cells is one of the best predictive markers for progression toward AIDS, and it is closely linked to CD4(+) T cell depletion and sustained viral replication. Aberrant activation of T cells is observed mainly for memory CD4(+) and CD8(+) T cells and is documented, in addition to increased expression of surface activation markers, by increased cell cycling and apoptosis. Notably, the majority of these activated T cells are neither HIV specific nor HIV infected, and the antigen specificities of hyperactivated T cells are largely unknown, as are the exact mechanisms driving their activation. B cells are also severely affected by HIV-1 infection, which is manifested by major changes in B cell subpopulations, B cell hyperactivation, and hypergammaglobulinemia. Similar to those of T cells, the mechanisms underlying this aberrant B cell activation remain largely unknown. In this review, we summarized current knowledge about proposed antigen-dependent and -independent mechanisms leading to lymphocyte hyperactivation in the context of HIV-1 infection.
authors.affiliation: Institute of Microbiology, ETH Zurich, Wolfgang-Pauli-Str. 10, HCI G401, 8093 Zurich, Switzerland.
authors.forename: Anna
authors.initials: A
authors.lastname: Haas
authors.forename: Kathrin
authors.initials: K
authors.lastname: Zimmermann
authors.forename: Annette
authors.initials: A
authors.lastname: Oxenius
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D011956:Receptors, Cell Surface / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology
chemical_list: D011956:Receptors, Cell Surface