In vitro immune responsiveness of rats lacking active dipeptidylpeptidase IV.

DPPIV (CD26) is a cell surface serine exoprotease recently described as a T cell activation molecule. A substrain of German Fischer 344 rats expressing a truncated, inactive form of DPPIV were used to determine whether the absence of enzymatic activity affected the overall immunological competence of these rats as compared to American Fischer 344 rats that express normal levels of DPPIV activity. The proliferative responses of splenic leukocytes obtained from both strains of rats were assessed in vitro following stimulation by T cell (Con A), B cell (LPS), and T and B cell (PWM) mitogens. In addition, proliferation was determined in the presence and absence of N-MMA, an inhibitor of nitric oxide production which is known to be a potent regulator of lymphocyte proliferation in vitro. Finally, the ability of these rats to produce a secondary response to KLH-primed lymphocytes was compared. No significant differences were found between the magnitude of either the mitogen or antigen-driven responses of immune cells obtained from American and German rats. The response to restimulation by KLH resulted in equivalent levels of KLH-specific immunoglobulin and IFN-gamma production as well. Taken together, these findings demonstrate that the proteolytic activity of DPPIV may not be necessary for the generation of immune competence or that in the absence of functional DPPIV, German Fischer rats have developed a compensatory proteolytic mechanism.