Immunological reactions induced by intracerebral transplantation: Evidence that host microglia but not astroglia are the antigen-presenting cells

Abstract

The immunological reactions to embryonic cerebellar xenografts ( n = 16) and allografts ( n = 8) in host rat brain were studied after 2, 4, and 6 weeks of survival and compared to a control group consisting of 10 rats with isografts. Indirect immunofluorescence was performed on fresh frozen brain sections using antibodies against antigen presenting cells (Ia/Ox-6+ cells) and T helper (W3/25+) cells. Massive infiltrations of both cell types were found within xenografts. Ia antigen was present in the walls of small vessels near the transplant as well as in the ventricles on supra- and subependymal cells. In host tissue surrounding the grafts, Ox-6+ immunoreactivity was also observed in a population of cells ranging from an irregular rod-like shape with short branching processes to more rounded cell bodies with retracted processes. The appearance of these cells was characteristic of microglia. These cells were GFAP-negative. These cellular reactions were associated with rejection of the grafts. In contrast, the allografts survived, but nevertheless cells expressing Ox-6+ and to a lesser extent W3/25+ immunoreactivity were found along the injection needle tract and in damaged host tissue surrounding the grafts. No Ox-6+ perivascular infiltrations were seen. Some staining was also found within the allografts, mainly associated with damaged tissue. Ox-6+ ramified cells were also observed. Both Ox-6+ and W3/25+ immunoreactivity decreased with the time of survival. Host and donor GFAP-positive astrocytes did not express Ox-6+ molecules, and therefore probably were not involved in presenting antigen to effector cells. The control isografts also survived very well, but nevertheless Ox-6+ and less widespread W3/25+ cells were present in surrounding injured host tissue. Ox-6+ perivascular infiltration was not found in the host brain of animals with isografts. Ox-6+ and W3/25+ immunoreactivities were present primarily in graft areas that appeared damaged, often closely associated with injured host tissue. These results indicate that the process of implantation of grafts and associated brain injury induces enhanced Ia/Ox-6+ immunoreactivity, primarily on microglia in brain parenchyma surrounding grafts, and suggest that host microglia may substantially contribute to the initiation of immune reactions against intracerebral grafts. Despite this predisposition to an immunological response, only in the case of xenografts did these reactions, with the addition of Ox-6+ perivascular cuffing and cell infiltrations within the grafts, lead ultimately to graft rejection.