Anti-idiotypic monoclonal antibodies (mAb) to an anti-CD4 mAb induce CD4+ T cell depletion in rabbit.

Abstract

We previously produced and characterized the syngeneic anti-idiotypic (Ab2) mAb F11-2302, F16-14D6 and F16-16D7 elicited with the mouse anti-human CD4 mAb HP2/6. We showed that F11-2302, which reacts with an idiotope (id) outside the antigen (Ag) combining site, fails to induce anti-CD4 antibodies (Ab) in mice, whereas mAb F16-14D6 and F16-16D7 to an id within (or closely related to) mAb HP2/6 Ag-combining site induces Ab to CD4 molecule. In the present investigation we extended our analysis to the immune response induced by these three mAb in a xenogeneic system by immunizing three New Zealand White (NZW) rabbits with Ab2 mAb. The latter animals were selected since rabbit CD4 molecules displayed a weak cross-reactivity with the anti-human CD4 mAb HP2/6. An additional rabbit was not immunized and used, together with the F11-2302-immunized one, as control. The three rabbits developed Ab3 Ab highly restricted to their respective immunizing mAb. Although no Ab reacting with human CD4 were detected in the three affinity-purified Ab3 preparations, a marked decrease in the percentage of CD4+ T cells was observed in the rabbits immunized with mAb F16-14D6 and F16-16D7. The results suggest that active specific immunotherapy with selected Ab2 mAb may induce biological effects similar to those generated by the passive administration of anti-CD4 mAb, and the rabbit could be an appropriate xenogeneic host for the testing of potential applications of anti-CD4 Ab2 mAb active immunotherapy in transplantation and autoimmune diseases.