Failure of freshly inplanted alloantigen in vivo to attract circulating allosensitized lymphocytes

Abstract

The important role served by donor-specific T lymphocytes in allograft rejection is well accepted. However, the mechanisms that attract the first alloreactive T cells to the graft are unclear. This study was performed to determine whether circulating specifically sensitized lymphocytes are attracted to alloantigen expressed on the surface of donor cells prior to the initiation of inflammatory reactions by the host. 111Indium-oxine labeled, bulk sensitized lymphocytes were injected intravenously into syngeneic mice bearing allogeneic and syngeneic peritoneal exudate cells in opposite hind footpads. Initially, twice as many sensitized lymphocytes were attracted to feet bearing the syngeneic peritoneal cells rather than the allogeneic peritoneal cells. In fact, the activity recovered from the allogeneic peritoneal cell depot was no greater than a contralateral footpad bearing media alone. This selective recruitment was present as early as 30 min following the transfer of radiolabeled cells. Furthermore, the labeled specifically sensitized lymphocytes were attracted to syngeneic macrophages within the peritoneal cell population. No other syngeneic and no allogeneic cells, at all, were capable of attracting circulating sensitized cells. Like specifically sensitized lymphocytes, thymocytes and concanavalin A blasts preferentially homed to sites of syngeneic macrophage deposition. Finally, clones of allospecific cytolytic and helper T cells also failed to migrate to sites of the specified donor alloantigen deposition. Thus, highly immune T cells accumulated, preferentially at sites of syngeneic macrophage inoculation. There is therefore no evidence to support the hypothesis that circulating specifically sensitized lymphocytes are attracted to alloantigen in vivo. Rather, it appears that the initial attraction of specifically sensitized, as well as unsensitized, lymphocytes is directed toward syngeneic macrophages. These data lend support to the hypothesis that the development of alloimmunity within the allograft may be initiated by host macrophages participating in normal healing responses.