Aerosolized anti-T-cell-receptor antibodies are effective against airway inflammation and hyperreactivity.
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.
Lahn
Michael
M
Department of Immunology, National Jewish Medical and Research Center, Denver, Colo, USA.
Kanehiro
Arihiko
A
Hahn
Youn-Soo
YS
Wands
J M
JM
Aydintug
M Kemal
MK
O'Brien
Rebecca L
RL
Gelfand
Erwin W
EW
Born
Willi K
WK
D000280:Administration, Inhalation; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology* / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000918:Antibody Specificity / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000097:blood / Q000139:chemically induced / Q000276:immunology*; D001991:Bronchitis / Q000097:blood / Q000139:chemically induced / Q000276:immunology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D008168:Lung / Q000166:cytology / Q000187:drug effects; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D016210:Methacholine Chloride / Q000008:administration & dosage / Q000009:adverse effects; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000008:administration & dosage / Q000009:adverse effects; D011948:Receptors, Antigen, T-Cell / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000097:blood / Q000139:chemically induced / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000378:metabolism
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta; D016210:Methacholine Chloride; D010047:Ovalbumin