Proliferation and migration of grafted hemopoietic cells during a graft-versus-host reaction induced by minor non-H-2 histocompatibility antigens in the mouse.

In our model of GVHR, irradiated (DBA/2 X B10.D2)F1 mice were given splenic and bone marrow cells from B10.D2 donor mice. At different set times after the graft, recipient mice were given a single injection of a radioactive precursor of DNA (125IUdR) and killed one hour later. The radioactivity in excised organs reflected the label incorporation by the proliferating cells. When mice were killed from 1 hour to 96 hours after the label injection the residual radioactivity in individual organs reflected the number of the residual living cells arising from cells which were in S-phase during the label pulse. This study allowed us to specify the dynamics of the cell proliferative activity and the behavior of these proliferating cells through the whole organism at any time of a GVH disease. A very interesting point is that the minor non-H-2 histocompatibility antigens (MiHA) responsible of the GVHR induced a very important and specific stimulation of the grafted cell proliferation in all the non-lymphoid organs with a spatial and timing evolution through the whole organism. A great part of the cells specifically stimulated to divide by the MiHA are very short-lived. The remaining living cells migrate out of the spleen and bone marrow and accumulate into the non-lymphoid organs after a latency period lasting 12-24 hours following the label uptake. This cell invasion was mainly into the liver, vesicular glands, kidneys, salivary glands and lungs.