Article

Aerosolized anti-T-cell-receptor antibodies are effective against airway inflammation and hyperreactivity.

Department of Immunology, National Jewish Medical and Research Center, Denver, Colo, USA.
International Archives of Allergy and Immunology (Impact Factor: 2.43). 06/2004; 134(1):49-55. DOI: 10.1159/000077533
Source: PubMed

ABSTRACT Aerosolized monoclonal antibodies (mAbs) specific for T-cell receptors (TCR) were used to manipulate T-cell function in airways of ovalbumin (OVA)-sensitized and -challenged mice with airway hyperresponsiveness (AHR). The inhaled mAbs were found to be effective at low doses, had little or no systemic effect and specifically abrogated both effector and regulatory functions of the targeted T cells. Specific mAbs targeting alphabeta T cells suppressed and those targeting gammadelta T cells enhanced AHR. Moreover, specific mAbs directed against subsets of gammadelta T cells varied in their effect on AHR. Using this approach of targeting either alphabeta or gammadelta T cells reduced airway eosinophila, although the effect of mAbs specific for alphabeta T cells was stronger. The use of aerosolized anti-TCR mAbs may offer an effective approach for the treatment of airway inflammation and AHR.

0 Followers
 · 
114 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Tissue eosinophil infiltration, which is a hallmark of allergic and helminthic diseases, is mainly coordinated by T lymphocytes, via the production of eosinophilotactic chemokines. Among T lymphocyte subsets, lymphocytes expressing γδ T cell receptor have been determined as a key factor for eosinophil accumulation via direct and indirect mechanisms. This knowledge is strongly supported by the fact that, in different experimental models of eosinophilic airway inflammation and helminth-induced Th2 lung inflammation, an evident tissue accumulation of γδ T lymphocytes is observed. In addition, the depletion of γδ T lymphocytes is correlated with the impairment of eosinophil accumulation in inflamed tissue. γδ T lymphocytes are non-conventional T lymphocytes, which comprise a minor T lymphocyte subset, mainly distributed in the tissue, and present crucial roles in innate and acquired immune responses. γδ T lymphocytes recognize several danger- and pathogen-associated molecular pattern molecules and stress antigens in a MHC-independent fashion and can provide rapid tissue-specific responses, via the production of a wide range of chemical mediators capable to modulate other cell populations. These mediators include chemoattractant cytokines and chemokines that attract eosinophils into the tissue by either direct recognition (such as IL-5, CCL11/eotaxin), or indirect mechanisms via the modulation of αβ T lymphocytes and macrophages (through the production of interferon-γ, IL-4, and CCL2/Monocyte chemoattractant protein-1, MCP-1, for example). The present review presents an overview of how γδ T lymphocytes coordinate eosinophil accumulation in allergy, by focusing on their role in airway inflammation and by discussing the involvement of cytokines and chemokines in this phenomenon.
    Frontiers in Pharmacology 12/2012; 3:200. DOI:10.3389/fphar.2012.00200
  • [Show abstract] [Hide abstract]
    ABSTRACT: Respiratory syncytial virus (RSV) infection has been hypothesized to be a risk factor for the development of allergy and asthma, but epidemiologic studies in humans still remain inconclusive. The association between RSV infection and allergic diseases may be dependent on an atopic background and previous history of RSV infection. It has been reported that RSV infection before sensitization to an allergen decreased the production of Th2-like cytokines in the lung and the levels of allergen-specific Th2-type antibodies in the serum. However, the underlying mechanisms are largely unknown. In the present study, the role of pulmonary γδ T cells in RSV-affected, allergen-induced airway inflammation was investigated. BALB/c mice were sensitized to or challenged with ovalbumin (OVA) and infected with RSV either before or after the sensitization period. It became clear that sensitization and challenge of mice with OVA induced a large influx of γδ T cells to the lungs. However, prior RSV infection inhibited the infiltration of γδ T cells as well as activated γδ T cells, characterized by expression of CD40L or CD69 molecular in the cell surface. Moreover, prior RSV infection elevated the type 1 cytokine gene expression but suppressed type 2 cytokine expression in the lung γδ T cells. Adoptive transfer of γδ T cells from OVA-sensitized and challenged mice increased airway inflammation, suggesting that γδ T cells may play a proinflammatory role in allergic responses. These results described here support the idea of an unknown γδ T cell-dependent mechanism in the regulation of RSV-affected, allergen-induced allergic airway responses. J. Med. Virol. 85:149-156, 2012. © 2012 Wiley Periodicals, Inc.
    Journal of Medical Virology 01/2013; 85(1):149-56. DOI:10.1002/jmv.23435 · 2.22 Impact Factor