Author:

Keywords:

11 Medical and Health Sciences, Respiratory System, 3201 Cardiovascular medicine and haematology, 3202 Clinical sciences

Abstract:

Previously, we showed, using SCID mice, that lymphocytes play an important role in a model of chemical-induced asthma. We investigated whether adoptive transfer studies would confirm the role of lymphocytes during sensitization. BALB/c mice where dermally sensitized on day 1 and 8 with 0.3% toluene-2,4-diisocyanate (TDI) or vehicle (acetone/olive oil) (20 µl/ear). On day 15, these mice were sacrificed and auricular lymph nodes were processed to obtain a cell suspension. These cells (0.5 x 106 or 1 x 106 cells) were injected intravenously into naïve mice. Three days later they received an intranasal challenge with 0.1% TDI or vehicle. Early airway response (Penh) was measured immediately after the challenge. One day later methacholine reactivity was assessed and the mice were sacrificed for cellular and immunological analysis in broncho-alveolar lavage (BAL) fluid. Naïve mice receiving lymphocytes from TDI-sensitized mice showed a three fold increase in early ventilatory response, compared to control mice, when challenged three days after passive sensitization. We found only a slight airway hyperreactivity in these mice. Nevertheless, they showed clear signs of airway inflammation in BAL, mainly characterized by an influx of neutrophils (20 %). We were able to passively sensitize naïve mice with lymphocytes from TDI-sensitized mice and this yielded an asthmatic response after an airway challenge. These experiments are the onset of a series of experiments in which subpopulations of specific lymphocytes will be transferred to define which lymphocyte types are most important in the development of chemical-induced asthma.