Requirement of adherent/phagocytic cells for the induction of F1 anti-parent cell-mediated lympholysis. I. Parental adherent splenocytes serve as stimulators.

Primary F1 hybrid anti-parent T cell-mediated lympholysis (F1 alpha P CML), induced in mixed spleen cell cultures, is an immune response specific for self H-2 antigens. The cellular requirements for induction were investigated by depleting or enriching stimulator splenocytes of adherent/phagocytic cells. Relatively large numbers of parental cells that are adherent to Sephadex G-10 particles or to plastic surfaces, and phagocytic for carbonyl iron, were required for stimulation (approximately 10(5) purified stimulators for 3.5 X 10(6) responders). Such parental cells are resistant to gamma radiation (in vivo and in vitro) and hydrocortisone (in vivo), negative for Thy-1, and positive for I-A and I-E/C surface antigens. This subpopulation of macrophages includes the predominant or sole immunogenic parental cell type of the spleen for the F1 alpha P response. Whereas removal of adherent/phagocytic cells from parental splenocytes entailed loss of stimulatory activity for F1 responder T lymphocytes, this was not the case for allogeneic responders. The ability to induce allogeneic CML was, in fact, fully retained by depleted parental cells. Adherent/phagocytic cells of F1 responder origin were available for cellular interactions in all mixed spleen cultures, yet they were competent for presentation of alloantigens, but not of self antigens borne by parental cells other than macrophages. In conclusion, the cellular requirements for stimulation differ quantitatively and qualitatively in F1 alpha P CML as compared to allogeneic and other CML systems. The distinct requirements presumably relate to the generation of specific effectors that are autoreactive as opposed to reactive with foreign antigens.