INDUCTION OF HOMOGRAFT TOLERANCE IN SUBLETHALLY X-IRRADIATED ADULT MICE

Technical Report · Mon Aug 19 04:00:00 EDT 1963

OSTI ID:4629087

Davis, W E; Cole, L J

It is now established that long-lived radiation chimeras, produced after the exposure of mice to lethal whole-body x radiation and infusion of allogeneic bone marrow cells are specifically tolerant to donor-type skin homografts. However, these tolerant mice represent the minority of animals thus treated which survive the secondary disease syndrome. The objective, therefore, has been to attempt to achieve homograft tolerance in sublethally irradiated adult mice under conditions that avoid secondary disease. Allogeneic mice which share the same H- 2 locus, but differ at other histocompatibility loci, have now been used with some success. A tolerant state has been produced in CBA (H-2K) mice by first exposing them to sublethal x radiation (500 rad) or urethan treatment coupled with irradiation, and then injecting C3H (H-2K) spleen (18 x 10/sup 6/) and/or bone marrow (42 x 10/sup 6/) cells within 3 days post irradiation. These mice have retained subsequent C3H skin homografts (over 165 days) but have rejected BALB/c skin grafts (H-2d) within 33 days. On the other hand, irradiated and urethan-treated controls, uninjected or injected with x ray inactivated (2000 rad in vitro) C3H cells, rejected both C3H and BALB/c homografts by 70 days. Similar results, although less definitive, have been obtained using C3H (H-2/sup k/) or BALB/c (H-2/sup d/) as the recipient mice and CBA (H-2/sup k/) or DBA/2 (R-2/sup d/) mice, respectively, for the donor cells. Such procedures, however, have been unsuccessful in producing homograft tolerance between donor and host F/sub 1/ hybrid mice which have one H-2 histocompatibility locus in common but differ at the other, ior example, CAF/sub 1/ (H-2/sup d+a/) and LAF/sub 1/ (H-2/sup b+a/. The significance of these results with regards to the requirement of cellular chimerism for the induction and maintenance of homograft tolerance is discussed. (auth)

• Research Organization: Naval Radiological Defense Lab., San Francisco
• NSA Number: NSA-17-038749
• OSTI ID: 4629087
• Report Number(s): USNRDL-TR-668
• Country of Publication: Country unknown/Code not available
• Language: English

Related Subjects

ANIMAL CELLS
BIOLOGY AND MEDICINE
BONE MARROW
CARBAMATES
CHIMERAS
ETHYL RADICALS
GENETICS
IMMUNITY
LETHAL DOSE
MICE
RADIATION DOSES
RADIATION EFFECTS
SENSITIVITY
SKIN
SPLEEN
TOXICITY
TRANSPLANTS
URETHANE
X RADIATION