The role of lymphocytes in antibody formation. I. Restoration of the haemolysin response in x-irradiated rats with lymphocytes from normal and immunologically tolerant donors.

Abstract

The haemolysin response of rats to an intravenous dose of 10 8 sheep erythrocytes was abolished by pretreatment with 500 rad of whole body X-irradiation. The immunological deficiency in such animals could be corrected equally well by either an injection of thoracic duct cells or by an inoculum consisting almost exclusively of small lymphocytes, obtained in each case from normal (non-immune) rats. The reversal of unresponsiveness depended upon the survival of the donor lymphocytes in the X-irradiated recipients and was not due to a non-specific restoration of the hosts’ own capacity to form antibody. Evidence for this conclusion came from experiments in which the X-irradiated recipients were themselves immunologically tolerant of sheep erythrocytes; additional support came from the inability of lymphocytes from immunologically tolerant donors to restore specific responsiveness in X-irradiated (non-tolerant) recipients. In a proportion of trials the immunological tolerance to sheep erythrocytes exhibited by thoracic duct lymphocytes from tolerant donors could be broken by incubating the cells in vitro before their injection into X-irradiated recipients. This points to the existence of individual tolerant cells in the tolerant populations of lymphocytes. Taken as a whole the experiments suggest strongly that small lymphocytes are the precursors of the cells which produce haemolysin against sheep erythrocytes in the rat.