William D. Kelly

AN INVESTIGATION OF HODGKIN'S DISEASE WITH RESPECT TO THE PROBLEM OF HOMOTRANSPLANTATION *

Homograft rejection is believed to be an immune phenomenon that in its general details most closely resembles that group of immune reactions commonly termed delayed hypersensitivity or allergy of the bacterial variety.l Our interest in Hodgkin’s disease was aroused by the reports of Schier and his co-workers*J that patients with Hodgkin’s disease are deficient in their ability to manifest this type of immune response. As a first step, experiments were carried out to attempt to confirm Schier’s observations; this work has been reported in detail el~ewhere.4.~ Skin testing was carried out in patients with histologically proved Hodgkin’s disease and in hospitalized controls, employing a standard battery of 7 antigens prepared from commonly encountered microorganisms to which the majority of individuals would be expected to react. The following materials were used: (1) dipththeria toxoid (Schick control solution), (2) streptokinase-streptodornase (SK-SD) , (3) mumps skin-testing antigen, (4) mumps control solution, (5) Trichophyton gypseum extract, ( 6 ) Candida albicans extract, and (7) purified protein derivative (PPD) of tubercle bacilli, intermediate strength. Testing was carried out in the conventional manner, injecting 0.1 ml. of suitable dilutions intradermally and noting the immediate reaction, if any, as well as the response a t 24 and 48 hours. A positive response was recorded if indurtion was present and if the reaction exceeded 5 mm. in diameter. To date 43 patients with Hodgkin’s disease have been tested; all but 1 of these patients were ambulatory a t the time of testing. None were receiving steroids or chemotherapy, although many were receiving regional X-ray therapy. The controls consisted of 208 hospitalized patients, excluding all individuals with malignancies or acute illness, as well as persons receiving treatment with steroids. The result of this testing is shown in TABLES 1 and 2. I t is apparent that patients with Hodgkin’s disease manifest a high incidence of nonreactivity or anergy in contrast to the controls. Our observations therefore confirm those reported by Schier and his co-workers. It then seemed logical to test the possibility that patients in whom delayed hypersensitivity is deficient might be anticipated to show tolerance or at least altered behavior to skin hornografts, since homograft rejection seems to resemble delayed hypersensitivity in respect to many details of the immune process. Accordingly, permission was obtained from a group of 17 patients with Hodgkin’s disease to carry out the placement of small skin homografts. These patients were all in fair to good general condition a t the time of grafting

Acquired tolerance to skin grafts induced with cell-free antigenic material, further tissue sources, frozen storage, dose-duration requirements.

Most C57BL/1 female mice normally reject male skin grafts. Tolerance to male skin grafts is induced in C57BL/1 female mice in most instances by the injection of cell-free tissue preparations obtained from spleen, liver, kidney, lung and heart. The potency of disrupted tissue preparations is generally well preserved by storage of tissue at deepfreeze temperatures for periods of 2–6 months. A notable exception to this observation in our experiments were the preparations of strored spleen. Tolerance to male skin grafts may be induced in the majority of C57BL/1 female mice by a single injection of 200–400 mg of cell-free antigenic material prepared from liver, spleen, kidney, heart and lung tissue as well as by the series of injections originally used which involved in aggregate 900 mg wet weight tissue equivalent. In the case of liver tissue, the administration of as little as 100 mg of cell-free antigenic material in a single injection has produced a high incidence of tolerance and a perceptible effect has been noticed at doses as small as 10 mg.

INDUCTION OF TOLERANCE TO SKIN GRAFTS IN MICE WITH DISRUPTED LIVER AND KIDNEY CELLS.

Summary Acquired immunological tolerance has been established in adult C57Bl/1 female mice to male skin grafts by injection of disrupted cellular material prepared from male liver and kidney as well as from spleen.