Effects of depletion of cells bearing the interleukin-2 receptor on immunoglobulin production and allergic airway responses in the rat.
Lymphocytes, key cells in chronic inflammation, are increased in the airways of asthmatics and have increased expression of the interleukin-2 (IL-2) receptor, a sign of activation. We determined the effects of depleting cells bearing IL-2 receptors on immunoglobulin (Ig) production, airway inflammation, and airway responses after antigen challenge of Brown Norway rats that were sensitized to ovalbumin (OA). Both control and ART-18 (antirat IL-2 receptor) antibodies inhibited plasma specific IgE and the early (ER) and late (LR) airway responses to antigen when given from zero to 14 d after sensitization. When ART-18 was administered from 4 to 14 d after sensitization and compared with control animals, it inhibited OA specific IgE production from Day 21 onward, but it increased total IgE and specific IgG. These changes followed a significant increase in blood CD4+ lymphocytes (%) in ART-18-treated animals 14 d after sensitization. The same protocol of administration did not affect Ig levels at 14 d, but it decreased neutrophil influx into the lungs 8 h after antigen challenge without any effects on the ER and LR. Administration of ART-18 at the time of antigen challenge did not affect the subsequent airway inflammation or the increased responsiveness to methacholine that occurs 32 h after antigen challenge. In summary, depletion of IL-2-receptor-bearing cells affects lymphocyte subsets and immunoglobulin production and it decreases the influx of neutrophils into the lungs 8 h after OA challenge, but it does not significantly inhibit the ER, LR, or increased airway responsiveness after antigen challenge.
Renzi
P M
PM
Respiratory Health Network of Centres of Excellence of Canada, Montreal, Quebec.
Yang
J P
JP
Diamantstein
T
T
Martin
J G
JG
D000818:Animals; D000911:Antibodies, Monoclonal; D001985:Bronchial Provocation Tests; D006967:Hypersensitivity / Q000276:immunology* / Q000503:physiopathology; D007136:Immunoglobulins / Q000096:biosynthesis*; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology*
D000911:Antibodies, Monoclonal; D007136:Immunoglobulins; D015375:Receptors, Interleukin-2