IgE-mediated downregulation of L-selectin (CD62L) on lymphocytes from asthmatic patients.

Abstract

L-selectin (CD62L) mediates the binding of lymphocytes to high endothelial venules of peripheral lymph nodes and is also involved in leukocyte attachment to the endothelium at sites of inflammation. Although it has been demonstrated that L-selectin is shed after lymphocyte activation, it is unknown whether the expression of L-selectin on the surface of lymphocytes can be modulated by an IgE-dependent mechanism or whether immunotherapy (IT) might affect this mechanism. One group of adult allergic asthmatic patients had received IT for the previous 3 years. Another similar group was not treated with IT. We challenged peripheral blood lymphocytes from both groups of asthmatic patients in vitro with an anti-IgE antibody (Ab). Expression of L-selectin on the lymphocyte surface was analyzed by flow cytometry, and the levels of soluble L-selectin (sL-selectin) on culture supernatant by ELISA. L-selectin was downregulated from the surface of lymphocytes in a time- and anti-IgE antibody dose-dependent manner (with a concomitant upregulation of shed L-selectin in the supernatant). When lymphocytes from non-IT asthmatic patients were cultivated with anti-IgE Ab, a statistically significantly greater CD62L downmodulation on the lymphocyte surface was observed compared with lymphocytes from the healthy group (P<0.002) and from the IT-asthmatic group (P<0.001). When lymphocytes from non-IT asthmatic patients were cultivated with anti-IgE Ab, a significantly greater sL-selectin level in the culture supernatant was observed compared with lymphocytes from the healthy group (P<0.001) and with lymphocytes from IT-asthmatic group (P<0.001). We present evidence that the expression of L-selectin on the surface of lymphocytes can be modulated by an IgE-dependent mechanism. This mechanism can be affected by IT.