Dipeptidyl peptidase IV (DP IV) activity in serum and on lymphocytes of MRL/Mp‐lpr/lpr mice correlates with disease onset

• Published in: Clinical and experimental immunology 1994-05, Vol.96 (2), p.292-296
• Main Authors: KUBOTA, T., IIZUKA, H., BACHOVCHIN, W. W., STOLLAR, B. D.
• Format: Article
• Language: English
• Subjects: Aging; Animals; Biological and medical sciences; Boron Compounds - pharmacology; CD26; Cell Membrane - enzymology; Dipeptidyl Peptidase 4; dipeptidyl peptidase IV; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases - analysis; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases - antagonists & inhibitors; double‐negative T cell; Enzymes - blood; Enzymes - drug effects; Female; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Histocytochemistry; Immunobiology; Lupus Nephritis - enzymology; Lymph Nodes - enzymology; Lymph Nodes - pathology; Lymphocytes - enzymology; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; Mice; Mice, Mutant Strains; MRL/Mp‐lpr/lpr mice; Pyrrolidines - pharmacology; serine protease; Spleen - cytology; Spleen - enzymology
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.1994.tb06556.x

SUMMARY DP IV (CD26), a serine protease expressed on activated T cells, participates in immune responses in vivo as well as in vitro. We measured cell surface and serum DP IV in mice of the autoimmune MRL/Mp‐lpr/lpr (MRL/1) strain, which is characterized by massive T cell proliferation and production of anti‐nuclear autoantibodies. The mass of inguinal lymph nodes correlated with scrum DP IV activity. Furthermore, serum DP IV activity increased markedly in parallel with the acceleration of lymph node swelling and anti‐nDNA antibody production. Serum DP IV activity in 16‐week‐old MRL/I mice reached levels up to three times higher than those in age‐matched MRL/Mp‐+/+ mice or BALB/c mice. Immunohistochemical staining and flow cytometric analysis identified DV IV on surfaces of lymphocytes from the enlarged lymph nodes of MRL/1 mice. Subcutaneous injection of the mechanism‐based inhibitor, Pro‐boroPro, reduced protease activity in serum and cell suspensions prepared from spleen and lymph nodes, confirming the identity of the enzyme as DP IV. These results indicate that the massively accumulating lymphocytes of MRL/1 mice have a property characteristic of activated T cells, although they express little surface CD4 or CD8 and do not produce IL‐2. DP IV may participate in the role these cells play in the pathogenesis of MRL/1 autoimmune disease.