A study in the plasma cell and lymphocyte reaction in rabbit tissue homografts

Abstract

The failure of tissue grafts from one animal to another of the same species (homografts) in mammals is known to result from an active immunization of the recipient animal. But attempts to show that circulating antibody is the agent of destruction have so far been unsuccessful. The present study was undertaken chiefly to test the widely entertained alternative hypothesis that the breakdown of these homografts is, in part at least, caused by the ‘lymphocytes’ whose infiltration into the graft is so characteristic a feature of the process. The method was to implant a set of grafts intradermally in each rabbit from a single donor and to excise one graft for histological study every fourth day thereafter. Sections stained with methyl-green pyronin were counted for lymphocytes and plasma cells (both m ature and presumptive im m ature). The cell counts were then subjected to various statistical tests. The invading cells were found to include, besides small lymphocytes, a large num ber of cells staining strongly with pyronin. Some of the latter were characteristic m ature plasma cells; the rest were, according to the evidence, probably im mature ones. The immature forms were largely lymphocytic in appearance, but some had reticular cell characteristics; m aturation occurred at the graft site. It appeared likely that a fate of the non-pyronin-staining lymphocytes was to become plasma cells; but others underwent destruction at the time of failure of the graft’s blood vessels. On the fourth day after implantation very few invading cells were present in the grafts. On the eighth day large numbers were present, and in most grafts the blood vessels were greatly dilated and engorged and tissue destruction was just beginning. At this time there was evidence of a positive relationship between the lymphocyte content of the grafts and the speed with which the grafts were going to be destroyed. No such relationship was found for the plasma cells. On the twelfth day the destruction was well advanced in most grafts and vascular breakdown widespread. No relationships were found between the concentrations of the invading cells and the stage of graft destruction achieved. But there was evidence that the increase in the number of m ature plasma cells in the grafts from the eighth to the twelfth day was positively related to the amount of graft tissue destroyed during that time; the lymphocyte increment, on the other hand, tended to be negatively related to the amount of tissue destroyed. It was seen that the percentage of im mature forms among the plasma cells was high in grafts at the beginning of breakdown and that it thereafter declined, but it tended to remain relatively high as long as graft tissue persisted. There was a positive relationship between this percentage in the grafts on the eighth day and the speed of graft breakdown. No graft was destroyed unless this percentage reached over fifty. It would appear to be an index of the progress of the host reaction against the graft. The grafts in one animal contained a massive infiltration of lymphocytes and plasma cells on the eighth and twelfth day without undergoing any tissue destruction. Lymphocytes were frequently observed in such close contact with the graft cells as to give the appearance of having penetrated them. Im m ature plasma cells were also found in such positions, but not frequently. Grafts were transplanted to animals previously sensitized by a set of grafts from the same donor. The second set of grafts in general underwent an accelerated destruction and had a much greater infiltration of plasma cells, but not of lymphocytes. Those second-set grafts which were slowest to breakdown contained most plasma cells. There was a striking correlation between the mature plasma-cell concentrations in an anim al’s first and second set of grafts, at any rate after graft breakdown was moderately advanced. It appeared that this cell concentration was determined by the response of the host animal rather than by the graft. Since the ranking of animals according to the speed of breakdown of their grafts was different for the first- and second-set grafts, this suggested that these cells were unlikely to be an important cause of graft destruction. In a few animals the second set of grafts was destroyed no quicker than the first set, yet their infiltration by plasma cells was much greater. This too was taken to be evidence against an important causative role for these cells. From these and other considerations it was concluded that the results do not support the hypothesis that the plasma cells which infiltrate these homografts are a significant cause of their destruction. The same would also appear to hold, though with less evidence, for the lymphocytes. At the same time it appeared likely that the plasma-cell response is specifically connected with the immune reaction. O f the m ain theories of plasma-cell function that of resorption would best explain the findings in these grafts. If the infiltrating plasma cells secrete specific antibody against the graft tissue this contribution to graft destruction would not appear to be significant.