Quantitative studies on tissue transplantation immunity - VI. Hypersensitivity reactions associated with the rejection of homografts

Abstract

If a guinea-pig R is sensitized by the transplantation of a skin homograft from a guinea-pig D, the intradermal injection into R of antigenic matter from D provokes an inflammatory response of delayed onset (direct reaction) that is outwardly and histologically similar to a tuberculin reaction. A reaction of the same kind is provoked when living cells expressed from the regional lymph nodes of R are injected intradermally into D (transfer reaction). The transfer reaction is interpreted as a local passive transfer of the state of reactivity dis­closed by the direct reaction. When due allowance is made for the sharing of antigens by members of outbred populations of guinea-pigs, both direct and transfer reactions are immunologically specific (§§ 2.3, 2.4, 3.1). The direct reaction can be provoked by cellular extracts (§ 2.3) as well as by living cells (§ 2-4). Its intensity is strongly correlated with the strength of the homograft reaction (§ 8). After sensitization by a single set of skin homografts, direct reactivity persists for a period of the order of hundreds of days (§ 4). ‘Hyperimmunization’ by the repeated injection of D cells into R is accompanied by a decline of direct reactivity (§ 6). The transfer reaction can be mediated through blood leucocytes (§ 3.2) and peritoneal exudate cells (§ 3.3) as well as by cells from lymph nodes. Although the regional node is the first node to be activated by a regional homograft, activity spreads thereafter to other nodes (§ 3.4). After the intravenous injection into R of 40 million lymphoid cells from D, transfer reactivity can be demonstrated in the leucocytes of R within 3 days (§ 3.2). Sensitized cells killed by heating, freezing or drying do not mediate the transfer reaction (§ 7.1). Extracts of leucocytes disrupted in the presence of deoxyribonuclease (Lawrence’s ‘transfer factor’) cannot deputize for living cells in the transfer reaction (§ 7.3), and evidence that such extracts can transfer direct reactivity to normal guinea-pigs is equivocal (§ 7.4). Disrupted leucocytes and especially blood platelets of syngeneic (‘isologous’) origin can give rise to violent non-specific delayed inflammatory reactions which resemble tuberculin reactions superficially but differ from them histologically (§ 7.3). Direct and transfer reactions were combined in an experiment in which cells or antigenic extracts from D were mixed with sensitized cells from R and then injected into a normal guinea-pig syngeneic with R (§ 3.5). Thus both direct and transfer reactions seem to depend essentially upon the local engagement of antigen with sensitized cells. Neither direct nor transfer reactions were affected by the administration of high doses of hydrocortisone (§ 5). It has not been possible to demonstrate direct or transfer reactions in mice, but the transfer reaction in rabbits is violent and prolonged (§ 3.0). (Other workers have demon­ strated direct reactivity in man.) The evidence, taken in the round, suggests that the delayed cutaneous inflammatory reactions revealed by the direct and transfer tests are manifestations of the homograft reaction, and not of an immunological reaction associated with some different iso-antigenic system. It thus supports the analogy long since drawn between the homograft and tuberculin reactions, and upholds the contention that the ‘second set’ homograft reaction reveals a pre-existing and not are-awakened (anamnestic) sensitivity (§ 8).