Acquired Tolerance to Skin Homografts in Mice* I. Histological Analysis of Lymphoid Tissues Be]~ore, During, and after the Loss of Tolerance by Bertie F. Argyris, Ph.d

Previously (1) it was demonstrated that, in the strain combination of mice under study, acquired tolerance to skin homografts was lost with increasing age. The chronic rejection pattern suggested a host versus graft reaction which increased in severity with time, culminating in the elimination of donor lymphoid cells and skin grafts. Since the rejection of homologous tissues by normal animals is accompanied by pronounced histological changes in the lymphoid organs of the host (2--4), the present studies were undertaken to detect similar histological indications of a host versus graft reaction in seemingly tolerant mice and to determine the onset of such a reaction. The strain combination used was particularly advantageous because a standard dose of 5 million adult CBA strain spleen cells, injected intravenously into newborn C3H mice, will result in 100 per cent tolerance without runt disease (5, 6). The high incidence of tolerance permitted the study of early stages in the development of tolerance, before test grafting of the injected animals was feasible. The absence of runt disease, believed to be a graft versus host reaction (5, 7, 8), avoided additional complications. Before a comparison between the lymphoid tissues of tolerant and nontolerant mice was possible, a detailed knowledge of the postnatal changes in normal lymphoid tissues was requisite. Although the prenatal development of the mammalian lymphoid system has been analyzed (9), and many studies have described normal or experimentally modified adult mouse lymphoid tissues (3, 10-13), we were unable to locate a detailed account of histological changes in the lymphoid tissues of the mouse during postnatal development. A description of the major changes which occur in the spleen, lymph nodes, thymus and liver of the C3H mouse from birth to old age was therefore included in this account. In addition to comparing the histological structure of lymphoid organs from control non-tolerant mice at various intervals after the tolerance-inducing