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Persistent immunogenicity of rat thymic epithelium
1Barbara Davis Center for Childhood Diabetes, Department of Microbiology and Immunology, University of Colorado Health Sciences Center, Denver 80262.
Culture of thymus tissue in 2-deoxyguanosine (2dGua) is thought to reduce tissue immunogenicity by selectively depleting highly immunogenic, thymic migrants of bone marrow origin. In the mouse 2dGua-treated thymus tissue survival is markedly enhanced compared with untreated tissue when transplanted under the kidney capsule of allogeneic recipients. These experiments were repeated in a rat model. As expected, DA strain neonatal thymus tissue was rejected when transplanted under the kidney capsule of normal allogeneic strain PVG rats. Surprisingly, acute rejection occurred when the tissue was cultured in 4 mM 2dGua, a dose capable of destroying rat thymocytes in vitro and 3 times the effective dose in mice. To test whether residual marrow-derived cells that escaped 2dGua treatment were responsible for inducing rejection, the treated DA tissue was "parked" in T cell-depleted PVG rats. Our working hypothesis was that the few remaining donor-derived cells of marrow origin would be overgrown by host-type cells. When 2dGua-treated DA thymus tissue was transplanted into T cell-depleted PVG recipients rejection did not occur. However this DA tissue, parked for as long as 200 days in T cell-depleted rats, was acutely rejected when retransplanted into normal PVG recipients. These results suggest that rat thymic epithelium devoid of marrow-derived cells in innately immunogenic.
Culture of thymus tissue in 2-deoxyguanosine (2dGua) is thought to reduce tissue immunogenicity by selectively depleting highly immunogenic, thymic migrants of bone marrow origin. In the mouse 2dGua-treated thymus tissue survival is markedly enhanced compared with untreated tissue when transplanted under the kidney capsule of allogeneic recipients. These experiments were repeated in a rat model. As expected, DA strain neonatal thymus tissue was rejected when transplanted under the kidney capsule of normal allogeneic strain PVG rats. Surprisingly, acute rejection occurred when the tissue was cultured in 4 mM 2dGua, a dose capable of destroying rat thymocytes in vitro and 3 times the effective dose in mice. To test whether residual marrow-derived cells that escaped 2dGua treatment were responsible for inducing rejection, the treated DA tissue was "parked" in T cell-depleted PVG rats. Our working hypothesis was that the few remaining donor-derived cells of marrow origin would be overgrown by host-type cells. When 2dGua-treated DA thymus tissue was transplanted into T cell-depleted PVG recipients rejection did not occur. However this DA tissue, parked for as long as 200 days in T cell-depleted rats, was acutely rejected when retransplanted into normal PVG recipients. These results suggest that rat thymic epithelium devoid of marrow-derived cells in innately immunogenic.