Skin Homograft Tolerance in Long-Lived Radiation Chimeras and Its Abolition by Injected Lymphoid Cells2

Abstract

(C57L × A) F₁ hybrid mice (LAF₁) were exposed to a lethal dose of X rays (870 r) and then received intravenous injections of mouse bone marrow cells obtained from genetically foreign normal donors (C3H strain). The mice that had survived for 1 year or more after this treatment were then challenged with tail-skin grafts to evaluate their immunological state. LAF₁ and C3H-type skin grafts (corresponding to the host and the marrow donor strains, respectively) were accepted by almost all the recipients. BALB/c- or DBA/2-type skin grafts (foreign to both the host and marrow donor strains) were rejected. These long-lived mice, known to be radiation chimeras, are therefore capable of a homograft response, but are tolerant to skin grafts of host (LAF₁) or of marrow donor (C3H) genotype. The tolerance to C3H skin grafts was abolished, and the C3H skin grafts were rejected 2 to 3 months after inoculation with lymphoid cells obtained from either normal or sensitized (anti-C3H) LAF₁ donors. Other chimeras, receiving injections of irradiated LAF₁ lymphoid tissue, maintained tolerance to the C3H skin grafts. To test for the presence of immunologically active C3H-type cells in these chimeras, cells from their lymphoid tissues were injected into sublethally irradiated (C3H × DBA/2)F₁ hybrids, and the signs of wasting and death known to follow the injection of parental strain C3H cells (but not LAF₁ cells) were observed. With this system, C3H lymphoid cells were present in the tolerant mice. In contrast, these cells were not present in the mice that were no longer tolerant to C3H grafts.