Timely blockade of ICAM-1.LFA-1 interaction prevents disease onset in a mouse model of emphysema.

Abstract

It is becoming apparent that emphysema is partly driven by self-reactive T cells inducing inflammatory damage. Thus, T cells become targets for therapy similar to other autoimmune diseases. Costimulatory blockade therapy targets disease-specific T cells, rendering them ineffective by blocking a necessary costimulatory event on the T-cell surface. This therapy is tested here in mouse emphysema. Peptides representing contact domains of counter receptors LFA-1 and ICAM-1 were used as blockade therapy in elastase-induced emphysema. When administered during the first week after disease induction, blockade prevented lung destruction, reduced leukocyte infiltration and inhibited the decrease in T-cell CD4:CD8 ratio, also common in human emphysema. Costimulatory blockade therapy can affect the progress of emphysema.