In vitro generation of human mixed lymphocyte culture suppressor cells. I. Cellular characterization and specificity.

The mixed leukocyte culture (MLC) of peripheral blood lymphocytes (PBLs) from two prospective kidney transplant recipients and their respective donors, produced a primed cell population that functioned as suppressors. The primed cells suppressed the primary and secondary MLC when added as third components, without demonstrable cytotoxic cells. Suppressor cells were derived from the MLCs of related pairs that were genotyped to be: (1) serologically defined (SD) identical and lymphocyte-defined (LD) nonidentical, and (2) HLA (total MHC) identical. Primed cells derived from MLC of unrelated HLA nonidentical subjects also showed similar effects. Two general patterns of inhibition were observed: a marked specific suppression of the autologous responding cells and, to a lesser degree, nonspecific suppression. The T cell fraction derived from the primed suppressor population was suppressive, the cells with B cell characteristics were not suppressive. The suppressive effect of cells generated in MLC was serially monitored after kidney transplantation. The suppressive activity of the primed cells was absent in the early postoperative period (4 weeks), perhaps because of high dose immunosuppression, but later in the course suppression was evident again (2 to 5 months). Manipulation of this T suppressor cell population may prove to be of value in enhancing graft acceptance.