Integrin-mediated epithelial-T cell interaction enhances nitric oxide production and increased intracellular inhibition of Chlamydia.

Abstract:

: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.

journal_name

J Leukoc Biol

authors

Igietseme JU,Uriri IM,Hawkins R,Rank RG

doi

10.1002/jlb.59.5.656

subject

Has Abstract

pub_date

1996-05-01 00:00:00

pages

656-62

issue

5

eissn

0741-5400

issn

1938-3673

journal_volume

59

pub_type

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