Abstract
Numerous reports in the literature indicate that there are immunosuppressive components in the alpha globulin fractions of human and murine sera (1, 2, 3, 4, 5, 6, 7, 8, 9). These investigations shed new insights on the mechanisms controlling immune responses in normal individuals, and may elucidate the specific mechanisms involved in producing immune deficiency disorders. | At least two possible mechanisms for immune suppression by serum alpha globulins have been proposed. The first hypothesis suggests that alpha globulins may coat immune lymphocytes , thereby preventing these cells from recognizing and reacting to antigens (2, 3, 4, 10, 11). Evidence for this hypothesis is based on experimental results in which the survival of skin homografts and transplanted tumors were prolonged in mice treated with homologous alpha globulins at the same time or shortly after the transplants were performed. | The second hypothesis postulates that immunoregulatory alpha globulin (IRA) prevents DNA synthesis (6). Supporting evidence for this mechanism stems from in vitro studies of H3 thymidine uptake by human lymphocytes following stimulation with either phytohemagglutinin (PHA) or specific antigens. | This present study was undertaken to evaluate the effects of human alpha globulins (Cohn Fraction IV) and/or sera from donors with a variety of pathological conditions on the response of cultured murine splenic lymphocytes to stimulation with either sheep erythrocytes (SRBC) or Concanavalin A (Con A). After establishing that alpha globulin did interfere with normal immune functioning of murine lymphocytes, the following additional questions were proposed: 1) is the alpha globulin toxic to murine lymphocytes; 2) does alpha globulin bind to the mitogen (SRBC or Con A), the lymphocyte, or both, thereby, interfering with their interaction; 3) does alpha globulin directly block DNA synthesis; if so, when during the mitogenic response does the suppression occur? | The rationale in determining the presence of immunosuppressive activity in patient sera was supported by reports (12, 13, 14) of impaired immune function in individuals with elevated levels of serum alpha globulins. Since the results of preliminary studies in our laboratory indicate that alpha globulin interferes with the normal immune functioning of murine lymphocytes, it seemed likely that such an assay system might prove to be of value in clinically screening patients' sera for such activity.