Aerosolized Anti-T-Cell-Receptor Antibodies Are Effective against Airway Inflammation and Hyperreactivity

National Research Center (CO, USA), Boulder, Colorado, United States
International Archives of Allergy and Immunology (Impact Factor: 2.67). 06/2004; 134(1):49-55. DOI: 10.1159/000077533
Source: PubMed


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.

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    • "It is however noteworthy that LPS-induced eosinophil accumulation is not mediated by either IL-5 or CCL11 (Bozza et al., 1994; Penido et al., 2001), even though γδ T lymphocyte migration triggered either by LPS or OVA requires CCL2 and LTB4 (Penido et al., 2003, 2008; Costa et al., 2010). In addition to the well established role of Vγ4+ T lymphocytes in murine models of airway hyperresponsiveness (Hahn et al., 2003; Lahn et al., 2004), the role of these cells in eosinophil migration has also been demonstrated (Lahn et al., 2004; Costa et al., 2009), reinforcing the notion that Vγ4 T cell subset plays a crucial role in tissue eosinophilia during allergic inflammation. "
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    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.
    Full-text · Article · Dec 2012 · Frontiers in Pharmacology

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    ABSTRACT: The resident population of T cells in the normal lung is small but during lung inflammation, T cells can increase dramatically. Histological analysis reveals diverse interactions between T cells and other pulmonary leukocytes. Studies in animal models show that T cells play a role in allergic lung inflammation where they can protect normal lung function, that they also are capable of resolving infection-induced pulmonary inflammation, and that they can help preventing pulmonary fibrosis. Lung inflammation threatens vital lung functions. Protection of the lung tissues and their functions during inflammation is the net-effect of opposing influences of specialized subsets of T cells as well as interactions of these cells with other pulmonary leukocytes.
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