Inhibition of IL 2 responsiveness of mitogen-stimulated lymphocytes by SMLR-generated plastic adherent suppressor cells

The proliferative response of spleen cells to concanavalin A (Con A) can be abrogated by plastic adherent suppressors generated in syngeneic mixed lymphocyte cultures of spleen cells. The addition of exogenously produced interleukins does not overcome the suppression, indicating that the suppressors are not simply competing for available growth factors. To examine the effect of the suppressors on IL 2 production and responsiveness, spleen cells were stimulated with Con A in the presence of the suppressors and assayed both for ability to produce IL 2 and for ability to bind IL 2. The culture supernates of suppressed spleen cells contained normal titers of biologically active IL 2, indicating that the suppressors do not inhibit IL 2 production or inactivate IL 2 after it is produced. Since IL 1 is required for IL 2 production, the failure of the suppressors to affect IL 2 production suggests that the suppressors have no effect on either production of, or responsiveness to, IL 1. The suppressed cells did, however, display a substantial reduction in ability to absorb IL 2 activity from a standard IL 2 preparation. The reduced frequency of IL 2 reactive cells did not appear to be due to a cytotoxic reaction insofar as no difference in viable cell recovery was noted between suppressed and nonsuppressed cultures at the time of assay. The suppressors therefore appear to inhibit the expression of IL 2 responsiveness without inhibiting the production of IL 2.