Abstract
Abstract The level of 3H-5-uridine (3H-Urd) incorporation by rat small lymphocytes (SL) taken from donors tolerant (T) or previously T to an allogeneic skin graft was monitored. DA rats were made T to Lewis (L) alloantigens by the injection at birth of semiallogeneic DA/L F1 bone marrow cells. Eight to 12 weeks after birth, allogeneic L skin was transplanted to the T rats. Animals accepting their skin graft for >100 days were either killed and 3H-Urd incorporation by SL from mesenteric lymph nodes (MLN) and spleen (SPL) was monitored, or the rats were injected with syngeneic DA MLN and SPL cells to abolish tolerance. Tolerance-abolished (TA) animals were killed and 3H-Urd incorporation was monitored autoradiographically at intervals before and after skin graft rejection. The level of graft-vs-host (GVH) reactivity of MLN cells from all T and TA rats was evaluated in a local popliteal lymph node GVH assay. T animals demonstrated a markedly depressed GVH reactivity when compared with control animals. Also, MLN SL from T rats autoradiographically exhibited 14.23 grains/SL, 226% above the average of 6.32 grains/SL observed in MLN SL from control animals. 3H-Urd incorporation by splenic SL from T rats was likewise elevated above control animals, representing a 221% increase. There was no increase in IgM+ cells in T vs. control animals. After i.v. injection of normal DA LN and SPL cells, the allogeneic grafts were rejected at 20 ± 2 days. However, from 15 to 21 days after the injection of syngeneic cells, the TA rat LN and SPL SL incorporated 3H-Urd at levels intermediate between those of T and control animals, but exhibited a level of incorporation not significantly different from controls 24 days after syngeneic cell injection. In addition, GVH reactivity of MLN cells taken from a T animal injected with syngeneic cells was restored gradually over a time period of >24 days. The fact that 3H-Urd levels are elevated in T animals indicates that an active phenomenon is related to the T state. The decrease in uridine incorporation during tolerance reversal provides further support for a metabolic change during tolerance that is different from that found in control animals.
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