Nitric oxide and T helper cell immunity.
In this article, the controversial role of nitric oxide (NO) in T helper (Th) cell activation and T-cell-dependent immunity will be discussed with an emphasis on immunosuppression by NO. NO is generated by antigen-presenting cells (APC) during the process of antigen presentation to T cells. In mouse models, activation of the inducible NO synthase (iNOS) in APC is triggered by Th1-cell-derived IFN-gamma, in combination with other soluble or membrane-associated T-cell factors. The NO so-produced inhibits T-cell proliferation, while it does not inhibit T cell cytokine production. NO blocks T-cell proliferation during G1/S transition. In mouse models of T-cell-mediated autoimmunity such as myelin antigen-induced EAE, the disease is exacerbated by genetic deletion of iNOS, indicating that NO suppresses T-cell-mediated immunity in vivo. Recent studies reveal that interaction with superoxide diminishes the T-cell regulatory activity of NO. The role for NADPH oxidase as a source for NO-inhibiting superoxide is discussed. In conclusion, NO plays an important regulatory role in the induction phase of T-cell-mediated immunity. Superoxide may enhance T-cell-mediated immunity by preventing the immunosuppressive activity of NO.
van der Veen
R C
RC
Department of Neurology, University of Southern California School of Medicine, Los Angeles 90033, USA. vanderve@hsc.usc.edu
D000818:Animals; D006801:Humans; D007111:Immunity, Cellular; D009569:Nitric Oxide / Q000502:physiology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism*
D009569:Nitric Oxide