Laboratory of Immunoregulation

Anthony S. Fauci, M.D., Chief

Director, NIAID

The major theme of the Laboratory of Immunoregulation (LIR) continues to be the elucidation of cellular and molecular mechanisms regulating the human immune response in health and disease. A major component of these efforts is the study of the immunopathogenic mechanisms of HIV infection and disease progression.

The rational design of strategies aimed at the prevention and treatment of HIV infection depends on delineating how HIV destroys the immune system. Our investigation of host factors involved in the evolution of HIV disease indicates that HIV pathogenesis is a multifactorial and multiphasic process. Particularly important aspects of this process that are under intense investigation include

• Regulation of HIV replication by endogenous cytokines and chemokines
• Regulation of expression of HIV coreceptors
• HIV envelope-mediated intracellular signaling events responsible for immune dysfunction
• The role of a latent, inducible reservoir of HIV-infected cells in the pathogenesis of HIV disease and its implication for antiretroviral therapy
• Contribution of HIV-infected T cells, B cells, dendritic cells, monocyte/macrophages, and multipotent progenitor cells to disease pathogenesis
• The role of immunomodulation in immune reconstitution during antiretroviral therapy for HIV infection
• LIR researchers conduct clinical trials to determine the safety and efficacy of drugs for the treatment of HIV infection and its complication and the development of methods for immunologic reconstitution in HIV-infected individuals. Their studies of the epidemiology and pathogenesis of HIV infection and other sexually transmitted diseases are both domestic and international.

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Major Areas of Research

• Cellular and molecular mechanisms of HIV immunopathogenesis
• Regulation of the human immune system, particularly the cellular and molecular mechanisms of activation, proliferation, and differentiation of human T- and B-cells
• Cellular gene expression during activation of human T and B cells
• Pathogenesis and treatment of immune-mediated diseases, particularly vasculitic syndromes