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Vol. 134, No. 1, 2004
Issue release date: May 2004
Int Arch Allergy Immunol 2004;134:49–55

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

Lahn M. · Kanehiro A. · Hahn Y.-S. · Wands J.M. · Aydintug M.K. · O’Brien R.L. · Gelfand E.W. · Born W.K.
Departments of aImmunology and bPediatrics, National Jewish Medical and Research Center, Denver, Colo., USA

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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 αβ T cells suppressed and those targeting γδ T cells enhanced AHR. Moreover, specific mAbs directed against subsets of γδ T cells varied in their effect on AHR. Using this approach of targeting either αβ or γδ T cells reduced airway eosinophila, although the effect of mAbs specific for αβ 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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  1. Hamelmann E, Oshiba A, Paluh J, Bradley K, Loader J, Potter TA, Larsen GL, Gelfand EW: Requirement for CD8+ T cells in the development of airway hyperresponsiveness in a murine model of airway sensitization. J Exp Med 1996;183:1719–1729.
  2. Lahn M, Kanehiro A, Takeda K, Joetham A, Schwarze J, Kohler G, O’Brien R, Gelfand EW, Born W: Negative regulation of airway responsiveness that is dependent on γδ T cells and independent of αβ T cells (see comments). Nat Med 1999;5:1150–1156.
  3. Carbone A, Harbeck R, Dallas A, Nemazee D, Finkel T, O’Brien R, Kubo R, Born W: Alpha beta T-lymphocyte depleted mice, a model for γδ T-lymphocyte functional studies. Immunol Rev 1991;120:35–50.
  4. Hahn YS, Taube C, Jin N, Sharp L, Wands J, Aydintug MK, Lahn M, Huber S, O’Brien RL, Gelfand EW, Born WK: Differential potentials of γδ T cell subsets in regulating airway responsiveness: Vγ1+ cells, but not Vγ4+ cells, promote airway hyperreactivity, Th2 cytokines, and airway inflammation. J Immunol 2004;172:2894–2902.
  5. Lahn M, Kanehiro A, Takeda K, Terry J, Hahn YS, Aydintug MK, Konowal A, Ikuta K, O’Brien RL, Gelfand EW, Born WK: MHC class I-dependent Vγ4+ pulmonary T cells regulate αβ T cell-independent airway responsiveness. Proc Natl Acad Sci USA 2002;99:8850–8855.
  6. Kon OM, Sihra BS, Compton CH, Leonard TB, Kay AB, Barnes NC: Randomised, dose-ranging, placebo-controlled study of chimeric antibody to CD4 (keliximab) in chronic severe asthma. Lancet 1998;352:1109–1113.
  7. Martin TR, Gerard NP, Galli SJ, Drazen JM: Pulmonary responses to bronchoconstrictor agonists in the mouse. J Appl Physiol 1988;64:2318–2323.
  8. Takeda K, Hamelmann E, Joetham A, Shultz LD, Larsen GL, Irvin CG, Gelfand EW: Development of eosinophilic airway inflammation and airway hyperresponsiveness in mast cell-deficient mice. J Exp Med 1997;186:449–454.
  9. Lahn M, Kalataradi H, Mittelstadt P, Pflum E, Vollmer M, Cady C, Mukasa A, Vella AT, Ikle D, Harbeck R, O’Brien R, Born W: Early preferential stimulation of γδ T cells by TNF-α. J Immunol 1998;160:5221–5230.

    External Resources

  10. Kubo RT, Born W, Kappler JW, Marrack P, Pigeon M: Characterization of monoclonal antibody which detects all murine αβ T cell receptors. J Immunol 1989;142:2736–2742.
  11. Goodman T, Lefrancois L: Intraepithelial lymphocytes: Anatomical site, not T cell receptor form dictates phenotype and function. J Exp Med 1989;170:1569–1581.
  12. Itohara S, Nakanishi N, Kanagawa O, Kubo R, Tonegawa S: Monoclonal antibodies specific to native murine T-cell receptor γδ: Analysis of γδ T cells during thymic ontogeny and in peripheral lymphoid organs. Proc Natl Acad Sci USA 1989;86:5094–5098.
  13. Pereira P, Gerber D, Huang SY, Tonegawa S: Ontogenic development and tissue distribution of Vγ1-expressing γδ T lymphocytes in normal mice. J Exp Med 1995;182:1921–1930.
  14. Dent AL, Matis LA, Hooshmand F, Widacki SM, Bluestone JA, Hedrick SM: Self-reactive γδ T cells are eliminated in the thymus. Nature 1990;343:714–719.
  15. Irvin CG, Bates JH: Measuring the lung function in the mouse: The challenge of size. Respir Res 2003;4:1–9.
  16. Bates JH, Irvin CG: Time dependence of recruitment and derecruitment in the lung: A theoretical model. J Appl Physiol 2002;93:705–713.
  17. Sehra S, Pynaert G, Tournoy K, Haegeman A, Matthys P, Tagawa Y, Pauwels R, Grooten J: Airway IgG counteracts specific and bystander allergen-triggered pulmonary inflammation by a mechanism dependent on Fc gamma R and IFN-gamma. J Immunol 2003;171:2080–2089.
  18. Lahn M, Kanehiro A, Takeda K, Konowal A, O’Brien RL, Gelfand EW, Born WK: γδ T cells as regulators of airway hyperresponsiveness. Int Arch Allergy Immunol 2001;125:203–210.
  19. Wyde PR, Wilson SZ, Kramer MJ, Sun CS, Knight V: Pulmonary deposition and clearance of aerosolized interferon. Antimicrob Agents Chemother 1984;25:729–734.
  20. Nadithe V, Rahamatalla M, Finlay WH, Mercer JR, Samuel J: Evaluation of nose-only aerosol inhalation chamber and comparison of experimental results with mathematical simulation of aerosol deposition in mouse lungs. J Pharm Sci 2003;92:1066–1076.
  21. Templin MV, Levin AA, Graham MJ, Aberg PM, Axelsson BI, Butler M, Geary RS, Bennett CF: Pharmacokinetic and toxicity profile of a phosphorothioate oligonucleotide following inhalation delivery to lung in mice. Antisense Nucleic Acid Drug Dev 2000;10:359–368.
  22. Zuany-Amorim C, Ruffie C, Haile S, Vargaftig BB, Pereira P, Pretolani M: Requirement for γδ T cells in allergic airway inflammation. Science 1998;280:1265–1267.
  23. O’Brien RL, Lahn M, Born WK, Huber SA: T cell receptor and function cosegregate in gamma-delta T cell subsets. Chem Immunol 2001;79:1–28.
  24. Kanehiro A, Ikemura T, Makela MJ, Lahn M, Joetham A, Dakhama A, Gelfand EW: Inhibition of phosphodiesterase 4 attenuates airway hyperresponsiveness and airway inflammation in a model of secondary allergen challenge. Am J Respir Crit Care Med 2001;163:173–184.
  25. Takeda K, Haczku A, Lee JJ, Irvin CG, Gelfand EW: Strain dependence of airway hyperresponsiveness reflects differences in eosinophil localization in the lung. Am J Physiol Lung Cell Mol Physiol 2001;281:L394–L402.
  26. Lee NA, Gelfand EW, Lee JJ: Pulmonary T cells and eosinophils: Coconspirators or independent triggers of allergic respiratory pathology? J Allergy Clin Immunol 2001;107:945–957.
  27. DiTirro J, Rhoades ER, Roberts AD, Burke JM, Mukasa A, Cooper AM, Frank AA, Born WK, Orme IM: Disruption of the cellular inflammatory response to Listeria monocytogenes infection in mice with disruption in targeted genes. Infect Immun 1998;66:2284–2289.
  28. Hahn YS, Taube C, Jin N, Takeda K, Park JW, Wands JM, Aydintug MK, Roark CL, Lahn M, O’Brien RL, Gelfand EW, Born WK: Vγ4+ γδ T cells regulate airway hyperreactivity to methacholine in ovalbumin-sensitized and challenged mice. J Immunol 2003;171:3170–3178.

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