Lymphocyte Responses Induced by Gammaglobulin Therapy

muno deficient children treated with commercially available preparations of gammaglobulin failed to proliferate and to mature into plasma cells in vitro after stimulation with pokeweed mitogen. The influence of the treatment on lymphocyte functions varied according to the cell population considered. A T helper cell activity was detected in these patients but only in the cell subset bearing receptors for IgG after irradiation. T lymphocytes exerted a suppressive effect that disappeared after irradiation or incubation at 37°C. The suppressive cells were found among E rosette-forming cells depleted of leukocytes bearing receptors for IgG. Their suppressive effect was expressed only in the presence of normal radioresistant T lymphocytes that did not bear Fc receptors for IgG. Similar dysfunctions could be induced in vitro by incubation ofnormal T and B lymphocytes with gammaglobulin preparations. Because F(ab)'2 fragments or deaggregated preparations of gammaglobulin failed to activate T suppressor lymphocytes, this activation was likely triggered by attachment of Fc portion of denatured IgG to the corresponding membrane receptor. This activation step was prostaglandinE2-dependent, suggestiing that activated monocytes were involved in the activation process. B lymphocyte responses appeared directly inhibited by attachment of denatured gammaglobulin oIn membrane Fc receptor. Our observations suggest that immunological effects of gammaglobulin therapy are not limited to antibody transfer, since it also indtices subtle rnodifications of in vitro pokeweed mitogenstimtulated T and B cell responses. These modifications nust be considered in interpreting results obtained in Received for publication 11 Februcaril 1980 anid in revised form 30 October 1980. immunodeficient patients investigated under gammaglobulin therapy.