Immunobiol., vol. 197, pp. 522-533 (1997) IDepartment of Biochemistry and Molecular Biology, University of Santiago de Compostela, Facultade de Bioloxia, 2the Immunology Service, Hospital Xeral de Galicia, Santiago de Com- postela, Spain Interleukin-12 Enhances C026 Expression and Oipeptidyl Peptidase IV Function on Human Activated Lymphocytes OSCAR J. CORDER0 1 , FRANCISCO J. SALGADO!, JUAN E. VINUELA 2 and MONTSERRAT NOGUEIRA! Received April 30, 1997· Accepted in revised form June 3, 1997 Abstract Research of a cellular pathway activated by IL-12 which may result in new therapeutical approaches for IL-12, led us to find an intriguing relationship between IL-12 and CD26/DPPIV ectopeptidase on activated T cells. Both the percentage and median fluorescence intensity (MFI) of CD26+ cells in the PHA-stimulated PBMC or lymphoblasts increased when IL-12 (optimum dose, 2 ng/m!) was present. Maximum CD26 expression was observed on day-2 cultures of Iym- phoblasts, the presence of IL-12 receptor probably being necessary for this up regulation. In addition, CD26 upregulation correlated with enhanced DPPIV function. Enzyme affinity and secretion of the soluble form of DPPIV were not affected by IL-12. Kinetic behaviours of Ag expression and enzymatic activity support a different CD26 regulation pathway by IL-12. These data suggest that the correlation found in vivo between the CD26 expression and Thl-like immune responses is due to this IL-12-dependent upregulation. Introduction The Ag-driven differentiation of T cells results in a series of changes in cell sur- face phenotype concomitant with their development into mature effector T cells. Among these changes is the alteration of expression of several cell-surface adhe- sion molecules that affect the interactions of T cells with other lymphocytes, with APC, with vascular endothelial cells, and with the extracellular matrix. Recent developments indicate that CD26 is a multifunctional molecule that may have these important roles in the immune system (1-6). The protease dipeptidylpeptidase IV (DPPIV, EC 3.4.14.5.), assigned to the CD26 cluster, is a glycoprotein localized in the plasma membrane of epithelial cells Abbreviations: ADA = adenosine deaminase; DPPIV = dipeptidyl peptidase IV; DPPT-L = large T cell DPPIV; MFI = median fluorescence intensity "1997 by Gustav Fischer Verlag