Inducible nitric-oxide synthase plays a minimal role in lymphocytic choriomeningitis virus-induced, T cell-mediated protective immunity and immunopathology

By using mice with a targetted disruption in the gene encoding inducible ni tric-oxide synthase (iNOS), we have studied the role of nitric oxide (NO) i n lymphocytic choriomeningitis virus (LCMV)-induced, T cell-mediated protec tive immunity and immunopathology. The afferent phase of the T cell-mediate d immune response was found to be unaltered in iNOS-deficient mice compared with wild-type C57BL/6 mice, and LCMV-induced general immunosuppression wa s equally pronounced in both strains. In vivo analysis revealed identical k inetics of virus clearance, as well as unaltered clinical severity of syste mic LCMV infection in both strains. Concerning the outcome of intracerebral infection, no significant differences were found between iNOS-deficient an d wild-type mice in the number or composition of mononuclear cells found in the cerebrospinal fluid on day 6 post-infection. Likewise, NO did not infl uence the up-regulation of proinflammatory cytokine/chemokine genes signifi cantly, nor did it influence the development of fatal meningitis. However, a reduced virus-specific delayed-type hypersensitivity reaction was observe d in iNOS-deficient mice compared with both IFN-gamma-deficient and wild-ty pe mice. This might suggest a role of NO in regulating vascular reactivity in the context of T cell-mediated inflammation. In conclusion, these findin gs indicate a minimal role for iNOS/NO in the host response to LCMV. Except for a reduced local oedema in the knockout mice, iNOS/NO seems to be redun dant in controlling both the afferent and efferent phases of the T cell-med iated immune response to LCMV infection.