Brief Definitive Reports SPECIFIC HETEROLOGOUS ENHANCEMENT OF IMMUNE RESPONSES* VI. PARTIAL PImI~ICATION OF A NONSPECIFIC ENHANCING FACTOR ]?ROM SITPERNATES OF ALLOGENEICALLY STIMULATED HUMAN LYMPHOCYTE

Interactions between cellular components of the immune system are mediated, at least in part, by macromolecular chemical signals or lymphokines. This is true both for cellular immunity (cf. 1, 2 for reviews), and for the humoral immune response (cf. 3, 4 for reviews). The first indication of the latter was described by Hartmann in 1970 (5), who reported enhancement of the number of plaque-forming cells (PFC) against sheep erythrocytes (SRBC) in vitro when T cells from animals primed with horse erythrocytes were added with horse erythrocytes and SRBC to normal spleen cell cultures. In 1971, Dutton et al. (6) reported that the supernatant fluid from mixed lymphocyte cultures of allogeneic mouse cells restored the plaque-forming cell responses of mouse spleen cultures depleted of T cells by antiserum. At the same time Rubin and Coons (7) confirmed and extended Hartmann's findings using tetanus toxoid and other antigens for "nonspecific" enhancement. Such enhancement is due to a factor released by sensitized lymphocytes upon renewed contact with antigen. Subsequent reports have confirmed and extended these findings (8). The enhancing factor (EF) liberated from primed mouse spleen or thymus cells by antigen or allogeneic stimulation had a mol wt, in our hands, of approximately 75,000 daltons as measured by gel filtration on both dextran and polyacrylamide bead columns (8). In this paper, we report the isolation of a soluble mediator from allogeneic mixtures of human lymphocyte cell lines which can nonspecifically enhance the humoral immune response of mouse spleen cells. This human enhancing factor