Cytokine-deficient mice as a model for generation of autologous anti-cytokine monoclonal antibodies.

The possibility of inducing immune responses to murine interleukin-4 (IL-4) and IL-13 and generating anti-cytokine monoclonal antibodies (mAbs) was studied in IL-4- and IL-13-knockout mice. The minimal doses of IL-4 or IL-13 that could induce significant anti-cytokine responses with titers of 5000-10,000 were 20 microg per injection with the total doses of 100 microg. The highest titers in a range of 20,480-40,960 were achieved by triple immunization of IL-13-knockout mice with 30 microg of IL-13 per injection. Anti-IL-4 mAbs were generated at an antibody serum titer about 400; however, only 0.5% of primary hybridoma clones were anti-IL-4-positive. Anti-IL-13 cell fusions were successful at titers of 20,480 and 40,960 with 50% of the primary clones positive. Both hybridomas secreted low-affinity IgMkappa mAbs and were IL-6-dependent. These data demonstrate that IL-4- and IL-13-deficient mice may develop high polyclonal immune responses to "syngeneic" murine cytokines but fail to generate high-affinity mAbs at the tested conditions.