Quantitative studies on tissue transplantation immunity. II. The origin, strength and duration of actively and adoptively acquired immunity

Abstract

In mice, as in other animals, the rejection of a skin homograft leaves its host in a state of heightened resistance, the effect of which is to hasten the rejection of a skin homograft transplanted on a second occasion from the same donor or from a donor genetically similar to the first. The median expectation of life of a first A-line skin homograft transplanted to a normal CBA host is 11·0 + 0·3 days; that of a second graft of A-line skin, transplanted within 60 days of the first graft, is reduced to 6 days or less. Immunity decays progressively over a period of months, but is still clearly in force after 120 days. The heightened resistance to second-stage grafts has the character of a secondary response. Normal CBA mice (‘secondary hosts’) which have been inoculated with certain tissues derived from actively immunized CBA mice (‘primary hosts’) behave thereupon as if they themselves had been actively immunized. The tissues of the primary host which have this power to transfer immunity are the regional lymph nodes and to a lesser degree the spleen. The regional nodes are therefore held to be the principal but not the only seat of the reaction against skin homografts. The efficacy of other pathways of response is revealed by the fact that extirpation of the regional nodes after the regression of a homograft does not impair the host’s capacity to give a secondary response; nor does extirpation of the regional nodes before grafting significantly reduce the power of the primary response—a result shown to be due not merely to the participation of other pre-existing centres of response, but also to the opening up of new pathways leading to lymph nodes which would not otherwise have taken part in the reaction. Killed lymph nodes and nodes transplanted subcutaneously had no power to transfer immunity; nor had massive doses of whole blood, blood leucocytes or serum. For these and other reasons, it is argued that the immunity acquired by the secondary hosts could not be due to the passive transfer of preformed antibodies. Nor could it be due to an active immunization of the secondary hosts by antigenic matter contained within the inocula taken from the primary hosts, for immunity can be transferred to CBA mice (‘tolerant mice') rendered incapable of reacting on their own behalf against the antigens which immunized the primary hosts. All the experimental findings are accounted for by the assumption that tissue transferred from the primary hosts survives and becomes incorporated in the secondary hosts, behaving in its new environment much as it would have done if left undisturbed in its environment of origin. The immunity that arises in this way is said to be adoptively acquired. Adoptive immunity is passive in the sense that it is of second-hand origin but active in that it depends upon the introduction and continued working of actively immunized cells. Adoptively immunized animals differ from passively immunized animals in being capable of a secondary response, and from actively immunized animals in never having given a primary response. The fact that transplantation immunity can be adoptively but not passively acquired argues in favour of its similarity to the tuberculin reaction and to sensitization reactions of the delayed type.