Dialysable nonspecific inhibitor of lymphocyte proliferation related to E-receptors (CD2)

Several investigators have pointed out that lymphocytic function may be profoundly affected by soluble factors occurring in human serum. It was observed, previously, that the addition of normal human serum dialysate (NHSD), at the beginning of lymphocyte cultures, inhibited the proliferative response to phytohemagglutinin (PHA) and to allogeneic cells. This suppressive effect was removed by previous absorption of NHSD with sheep erythrocytes (E). These data suggested that the dialysable fraction of human serum contains a suppressive factor, apparently related to the human T cell receptor for E (T11 or CD2). In this study we investigated at which phase of the proliferative response does the inhibition induced by NHSD take place. In order to confirm the relationship between this inhibitory factor and E-receptors, the NHSD was subjected to passage through a sepharose affinity column sensitized with an anti-E-receptor serum. This anti-E-receptor serum was obtained by immunizing a sheep with autologous E sensitized with human E-receptors. Time-course experiments showed that NHSD inhibited lymphocyte proliferation induced by PHA even when added to the cultures 18-24 h after mitogenic stimulation. In bidirectional mixed lymphocyte cultures the impairment of the proliferative response was inversely proportional to the time of NHSD addition. NHSD also inhibited the interleukin-2 (IL2) mediated proliferation of lymphoblasts previously exposed to PHA to ensure IL-2-receptors expression. The inhibitory effects of the NHSD were completely removed by absorption with E or by passing NHSD through the affinity column sensitized with the anti-E-receptor serum.(ABSTRACT TRUNCATED AT 250 WORDS)