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 mi ce. Recent evidence from studies in an in vitro model of the mucosal e pithelium, the polarized epithelial-lymphocyte coculture (PELC) system , indicated that protective murine T cells mediated intracellular inhi bition of the Chlamydia trachomatis agent of mouse pneumonitis (MoPn) at least partly by activating the interferon-gamma (IFN-gamma)-inducib le 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 iNO S. The results revealed that the ability of this clone to clear Chlamy dia in vivo is in part mediated by induction of nitric oxide (NO) prod uction. The L-arginine analogue and iNOS inhibitor, N-G-monomethyl-L-a rginine 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 hypothe sis that the IFN-gamma-inducible iNOS pathway is involved in the contr ol of Chlamydia by T lymphocytes in mice.