INTEGRIN-MEDIATED EPITHELIAL-T CELL-INTERACTION ENHANCES NITRIC-OXIDEPRODUCTION AND INCREASED INTRACELLULAR INHIBITION OF CHLAMYDIA

T cell-mediated immunity against Chlamydia in mice is mediated at leas t in part by T cell-derived interferon-gamma (IFN-gamma) induction of the nitric oxide synthase (iNOS) system in infected epithelial cells. Although IFN-gamma alone could stimulate nitric oxide (NO) production from epithelial cells and inhibit the intracellular growth of Chlamydi a, the effectiveness was less than when infected epithelial cells were co-cultured with IFN-gamma-producing T cell clones, In co-cultures co ntaining T cells and infected epithelial cells, additional NO produced by activated T cells could augment chlamydial killing; however, T cel l-derived NO was insufficient to account for the total NO present in t he co-culture and therefore could not explain the dramatic increase in chlamydial inhibition under those conditions, To determine whether di rect cell-to-cell interaction involving adhesion molecules was involve d in increased NO induction, the ability of neutralizing monoclonal an tibodies directed against intercellular adhesion molecule type 1 (ICAM -1) and leukocyte function antigen-1 (LFA-1) to suppress NO production and lower intracellular chlamydial inhibition was investigated, It wa s found that monoclonal antibodies against ICAM-1/LFA-1 could signific antly reduce the capacity of a protective CD4(+) type 1 (Th1) clone (c lone 2.14-0) to inhibit the intracellular growth of the C, trachomatis agent of mouse pneumonitis (MoPn). The suppression of the anti-chlamy dial action of the clone by antibodies correlated with similar to 50% decrease in NO production, Also, paraformaldehyde-fixed clone 2.14-0 c ould enhance NO induction and chlamydial inhibition mediated by IFN-ga mma, and this effect could be reversed by anti-ICAM-1/LFA-1 antibodies , The results indicated that epithelial-T cell interaction via adhesio n molecules enhances NO production and increased chlamydial inhibition by IFN-gamma-secreting T cells.