Molecular mechanism of T-cell control of Chlamydia in mice: Role of nitric oxide in vivo

T-cell-mediated immunity is crucial for the control of Chlamydia in mice. Recent evidence from studies in an in vitro model of the mucosal epithelium, the polarized epithelial-lymphocyte coculture (PELC) system, indicated that protective murine T cells mediated intracellular inhibition of the Chlamydia trachomatis agent of mouse pneumonitis (MoPn) at least partly by activating the interferon-gamma (IFN-gamma)-inducible nitric oxide synthase (iNOS) pathway. To investigate whether nitric oxide played a role in controlling chlamydial infection in vivo, the protective capacity of a chlamydial-specific T-cell clone (clone 2.14-0) was analysed in mice in the presence of a specific inhibitor of iNOS. The results revealed that the ability of this clone to clear Chlamydia in vivo is in part mediated by induction of nitric oxide (NO) production. The L-arginine analogue and iNOS inhibitor, N-G-monomethyl-L-arginine monoacetate (MLA), increased the chlamydial burden in infected mice and inhibited the ability of clone 2.14-0 to clear genital MoPn infection in vivo. The results are consistent with the working hypothesis that the IFN-gamma-inducible iNOS pathway is involved in the control of Chlamydia by T lymphocytes in mice.