STUDIES ON RADIATION-INDUCED CHIMERAS. EARLY DEVELOPMENT OF GRAFT-TO-HOST TOLERANCE. PREVENTION OF SECONDARY DISEASE BY ISOANTISERUM AND PRE-IRRADIATION OF MARROW DONOR
Radiation bone marrow chimeras were prepared by injecting marrow cells from adult C3H strain donors ina lethally x irradiated (880 rad) LAF/sub 1/ mice. It was found that spleen cells from these chimeras (removed 35 to 57 days postirradiation) did not reject either donor (C3H) or host (LAF/sub 1/) type marrow cells, when transferred a other lethally x irradiated recipients, but were able a reject marrow of a third inbred strain (BALB/c). Similarly, in a series of parental-F/sub 1/ hybrid lymphoid cell chimeas, spleen and lymph node cells from these chimeras (as early as 5 to 10 days after establishment of chimerism) in no instance elicited secondary disease deaths when transferred to new irradiated LAF/sub 1/ hosts. Yet these same cell populations were immunologically competent, as shown by their capacity to reject homologous (C3H strain) bone marrow. Thus, these cell populations have developed specific tolerance (i.e., nonreactivity) for their primary LAF/sub 1/ hosts as early as 1 week following initial transplantation. C3H marrow donor mice were exposed to a single sublethal dose of x rays (400 rad); 12 or 16 days later their marrow was removed and injected ina lethally x irradiated LAF/sub 1/ recipients (22 x 10/sup 6/ cells injected per mouse). The incidence of secondary disease deaths (at 120 days) in these series was 0 out or 11, and 1 out of 8; in controls which received marrow from nonirradiated C3H donors, 6 out of 17 were dead by 120 days. Two additional groups of bone marrow chimeras received intravenous injections of isoartiserum (arti-C3H) at 16 and 18 days, or at 46 and 48 days after marrow infusion. No secondary disease deaths were observed in 17 mice thus treated by 7 months postirradiation. It is concluded that specific graft-to-host tolerance may develop relatively early in radiation chimeras that it is possible to prevent or eliminate secondary disease in homologous radiation chimeras by suitable preirradiation of the marrow donors, and by injection into the chimeras of specific isoantiserum directed against the marrow donor. (auth)
- Research Organization:
- Naval Radiological Defense Lab., San Francisco
- NSA Number:
- NSA-16-021918
- OSTI ID:
- 4827681
- Report Number(s):
- USNRDL-TR-560
- Resource Relation:
- Other Information: Orig. Receipt Date: 31-DEC-62
- Country of Publication:
- Country unknown/Code not available
- Language:
- English
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