Nitric oxide and T helper cell immunity

In this article, the controversial role of nitric oxide (NO) in T helper (T h) 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 membra ne-associated T-cell factors. The NO so-produced inhibits T-cell proliferat ion, 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 a utoimmunity 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 di minishes the T-cell regulatory activity of NO. The role for NADPH oxidase a s a source for NO-inhibiting superoxide is discussed. In conclusion, NO pla ys an important regulatory role in the induction phase of T-cell-mediated i mmunity. Superoxide may enhance T-cell-mediated immunity by preventing the immunosuppressive activity of NO. (C) 2001 Published by Elsevier Science B. V.