INTERLEUKIN-2 FUSION PROTEIN (DAB(389)IL-2) SELECTIVELY TARGETS ACTIVATED HUMAN PERIPHERAL-BLOOD AND LAMINA PROPRIA LYMPHOCYTES

Activated mucosal T lymphocytes correlate with the intestinal inflamma tion of inflammatory bowel disease. Activated T cells elaborate interf eron-gamma (IFN-gamma) and express high-affinity interleukin-2 (IL-2) receptors. The IL-2/diphtheria toxin fusion protein (DAB(389)IL-2) has been shown to specifically kill high affinity IL-2 receptor-bearing c ells, We tested whether DAB(389)IL-2 could specifically target activat ed lamina propria lymphocytes, Lymphocytes were activated in vitro wit h phytohemagglutinin and IL-2 for 24-48 hr. Toxin efficacy was determi ned by the [C-14]leucine incorporation, IFN-gamma ELISA, and flow cyto metry. DAB(389)IL-2 (10(-11) M) inhibited protein synthesis by 80% in activated lamina propria lymphocytes, This inhibition was blocked by c oculture of either excess IL-2 or a nonfunctional IL-2 diphtheria toxi n mutant protein, DAB(389)IL-2 (10(-11) M) also significantly reduced the numbers of activated helper T cells and IFN-gamma levels in 24-hr cultures. DAB(389)IL-2 specifically targets activated IL-2 receptor-po sitive lamina propria lymphocytes and is a potential new therapeutic a gent for patients with active inflammatory bowel disease.