Fine specificity of antibodies produced in rhesus monkeys following in vivo treatment with anti-T cell murine monoclonal antibodies.

The immune response of 23 rhesus monkeys against different murine monoclonal antibodies (mAb) administered in vivo as immunosuppressive agents has been analyzed. Seven mAb specific for either helper-inducer (CD4 molecules) or cytotoxic/suppressor (CD8 molecules) T cells, that cross-react with monkey lymphocytes, were administered i.v. for 10 consecutive days in rhesus monkeys. Nineteen of the animals were recipients of a skin or renal allotransplant. Nineteen out of the 23 monkeys developed a significant immune response against the injected monoclonal. This response was restricted in its specificity since unrelated murine monoclonals were not recognized by the monkeys' anti-monoclonal immunoglobulins. Fine analysis of the monkeys' sera revealed that the antibodies produced against the xenogeneic proteins selectively exhibited two major specificities i.e., anti-isotypic and anti-idiotypic. On a practical basis, these results suggest that an animal already immunized against a given mAb should still be sensitive to the therapeutic effect of another monoclonal sharing the same specificity but different idiotype.