Integrin-mediated epithelial-T cell interaction enhances nitric oxide production and increased intracellular inhibition of Chlamydia.
T cell-mediated immunity against Chlamydia in mice is mediated at least 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 Chlamydia, the effectiveness was less than when infected epithelial cells were co-cultured with IFN-gamma-producing T cell clones. In co-cultures containing T cells and infected epithelial cells, additional NO produced by activated T cells could augment chlamydial killing; however, T cell-derived NO was insufficient to account for the total NO present in the co-culture and therefore could not explain the dramatic increase in chlamydial inhibition under those conditions. To determine whether direct cell-to-cell interaction involving adhesion molecules was involved in increased NO induction, the ability of neutralizing monoclonal antibodies 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 was found that monoclonal antibodies against ICAM-1/LFA-1 could significantly reduce the capacity of a protective CD4+ type 1 (Thl) clone (clone 2.14-0) to inhibit the intracellular growth of the C. trachomatis agent of mouse pneumonitis (MoPn). The suppression of the anti-chlamydial action of the clone by antibodies correlated with approximately 50% decrease in NO production. Also, paraformaldehyde-fixed clone 2.14-0 could enhance NO induction and chlamydial inhibition mediated by IFN-gamma, and this effect could be reversed by anti-ICAM-1/LFA-1 antibodies. The results indicated that epithelial-T cell interaction via adhesion molecules enhances NO production and increased chlamydial inhibition by IFN-gamma-secreting T cells.
Igietseme
J U
JU
Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
Uriri
I M
IM
Hawkins
R
R
Rank
R G
RG
D000818:Animals; D002450:Cell Communication; D002478:Cells, Cultured; D002689:Chlamydia / Q000276:immunology*; D018920:Coculture Techniques; D004847:Epithelial Cells; D005260:Female; D016023:Integrins / Q000502:physiology*; D007371:Interferon-gamma / Q000494:pharmacology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000502:physiology*
D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D009569:Nitric Oxide; D007371:Interferon-gamma