CD26 MEDIATES THE ACTION OF HIV-1 TAT PROTEIN ON DNA-SYNTHESIS AND CYTOKINE PRODUCTION IN U937 CELLS

The human immunodeficiency virus 1 (HIV-1) Tat protein is known to be capable of suppressing antigen- and CDS-induced activation of human T cells. Previously, it was shown that Tat can bind to the dipeptidyl pe ptidase IV (DP IV, CD26) and inhibit the degradation of the chromogeni c substrate Gly Pro-p-nitroanilide. Using the method of free zone capi llary electrophoresis, here we have shown that the DP IV-catalyzed hyd rolysis of the NH2-X-Pro-containing cytokine peptides IL-2 (1-12), IL- 1 beta (1-6), and IL-6 (1-12) was also significantly inhibited by the Tar protein. Moreover, HIV-1 Tat at a concentration of 10 mu g/ml was found to have a strong suppressive effect on DNA synthesis and IL-1 be ta production, but stimulates secretion of IL-1 receptor antagonist (I L-1RA) and TNF-alpha of CD26-expressing U937-H cells. It did not impai r neither DNA synthesis nor cytokine production of low CD26-expressing U937-L cells. Similar results have been found with synthetic DP IV/CD 26 inhibitors (Immunobiol., 1994, vol. 192, pp. 121-136). These data s trongly suggest that Tat protein is a potent natural, inhibitor of DP IV/CD26, and they support the hypothesis that DPIV plays a role in Tar 's immunosuppressive activity.