Tolerance induction by fusion of fetal thymus lobes in organ culture.

Abstract

Abstract The immunologic and cellular effects of early contacts between either syngeneic or allogeneic whole 14 day fetal thymus lobes in organ culture were studied. Both syngeneic and allogeneic fetal lobes rapidly fused to form a single organ. Syngeneic fusions produced two peaks of lymphoid cell growth on days 6 to 8 and 11 and 12 of culture, and these peaks followed peaks of 125IUDR incorporation. Allogeneic fusions also resulted in first peak lymphocyte production but failed to produce a second peak. 125IUDR studies confirmed the decrease of late cell proliferation. Studies with anti-H-2 sera showed that in allogeneic fusions both parental cell types were equally represented. Fusions of parental and semi-allogeneic lobes, however, produced both cell peaks, but only one in four of the cells contained the H-2 marker of the F1 type. Removal of cortisone-sensitive cells by exposure of the thymus lobes to 10-7 M hydrocortisone during the 1st week of culture did not prevent the loss of a second peak in allogeneic fusions. Similarly, when fusions were produced after 1 week of prior independent growth, allogeneic fusion also failed to produce a second peak. However, specifically alloreactive cytotoxic cells could not be consistently demonstrated in allogeneic fusions when tested against appropriate 51Cr-labeled tumor cells. In a one-way MRL assay, cells from allogeneic fusions failed to respond to irradiated spleen cells of either parental type but responded well against third-party cells.