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. Author manuscript; available in PMC: 2017 Sep 1.
Published in final edited form as: Transplantation. 2016 Sep;100(9):1907–1915. doi: 10.1097/TP.0000000000001290

Figure 3. Rejection of allogeneic hepatocytes transplanted directly to the liver (intraportal injection) readily occurs in the absence of recipient peripheral lymphoid tissue.

Figure 3

FVB/N hepatocytes (H-2q) were transplanted through intraportal injection into untreated wild-type hosts (WT; n=10), WT hosts with previous splenectomy (splx; n=6), LTα KO hosts (lacking peripheral lymph nodes; n=6), and LTα KO hosts with previous splenectomy (n=6; all H-2b). A) Graft rejection occurred with similar kinetics in all groups (MST=10 days; p=ns). CD8-depletion did not prolong graft survival in WT recipients (MST=day 14, n=4), whereas graft survival was significantly prolonged in CD8-depleted LTα KO recipients (MST>30; p<0.001; n=3). Prolonged graft survival was observed in WT recipients only following both CD4- and CD8-depletion (MST>30; p<0.001; n=4). B) Alloantibody production was evaluated in recipient mice on day 14 following transplantation. Following intraportal transplantation, WT recipients developed significant levels of alloantibody (titer=92±8; n=6) which was abrogated in CD4-deficient recipients (titer=12±2; n=5; p<0.001, signified by “*”) but remained intact despite splenectomy (splx; titer=75±14; n=4; p=ns). Significantly higher levels were observed following CD8-depletion in WT recipients (titer=1300±300, n=3, p<0.001 as compared to WT recipients, as signified by “**”). Alloantibody production was abrogated in WT recipients following CD4- and CD8-depletion (titer=8±2). Alloantibody was not detected in any lymph node deficient hosts (LTα KO; titer=13±3; n=4), LTα KO with splenectomy (splx; titer=9±1; n=4), or CD8-depleted LTα KO recipients (titer=13±3; n=3; p<0.001 for all groups compared to WT recipients, signified by “***”). The dotted line represents naïve serum control. C) CD8-mediated in vivo allocytotoxicity was readily detected in WT (87±4%; n=7), splenectomized WT (77±7%; n=4), LTα KO (53±6%; n=3), and splenectomized LTα KO recipients (34±5%; n=3) as compared to naïve controls (2±0.1%; p<0.01 for all, signified by “*”). In vivo cytotoxicity was significantly reduced but still detectable in CD8-depleted WT recipients (45±12%; n=3; p=0.04 compared to WT, signified by “**”). Cytotoxicity was only abrogated in WT recipients following both CD4- and CD8-depletion (0±0%; p<0.001). In contrast, CD8-depletion abrogated in vivo cytotoxicity in LTα KO recipients (5±2%; n=3; p=0.004, signified by “***”).