Acquired tolerance to CBA skin homografts is lost in a large number of C3H mice neonatally injected with CBA spleen cells. The skin homografts persist for at least 2 months but then exhibit a chronic rejection pattern which may last up to 7 months. Histological analysis of the lymphoid tissues reveals the onset of an immune response in the axillary lymph nodes of many 4-month-old tolerant mice. This immune response which appears before external indications of graft rejection are evident, is manifested as an increase in number of germinal centers and plasma cells in the cortex and medulla, respectively. In older tolerant mice, an even larger proportion show these histological indications of immunological activity. During graft contraction and shortly after graft rejection, the immune response is still limited to the lymph nodes. After rejection of a second graft by post-tolerant mice, histological indications of an immune response are not only found in lymph nodes but also in spleen.

The data suggest the development of a host versus graft reaction in seemingly tolerant C3H mice, which increases in severity with the age of the animal. The results are discussed from the point of view that tolerance is dependent upon a critical balance between the immune potential of the host and the population of donor cells. As mice mature, their immune potential may increase. The resulting host versus graft reaction increases, culminating in the rejection of skin graft and donor lymphoid cells.

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