Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of murine spleen cells (SpC) with L-leucyl-L-leucine methyl ester (Leu-Leu-OMe) depletes L3T4(+) and Lyt2(+) cytotoxic T lymphocyte precursors and the capacity to generate lethal graft-versus-host disease in semiallogeneic class I + II MHC and multiple non-MHC-disparate recipient mice, whereas T helper cell function is preserved. In the present studies the role of Leu-Leu-OMe-sensitive CTL in skin graft rejection was examined. C57BL/6J (B6) mice were serially thymectomized, lethally irradiated, reconstituted with T cell-depleted bone marrow, and treated with intraperitoneal injections of anti-L3T4 and anti-Lyt2 monoclonal antibodies. These adult thymectomized, bone marrow-reconstituted, T cell-depleted (ATXBM, TCD) mice were unable to reject B6xDBA/2F1 (B6D2F1) skin grafts. When such ATXBM, TCD mice were reconstituted with 7 x 10(7) control B6 SpC, acute rejection of B6D2F1 skin was observed. When B6 donor SpC were Leu-Leu-OMe-treated prior to transfer to ATXBM, TCD mice, uniform rejection of B6D2F1 skin grafts was still observed, although a significant delay in the time to rejection was observed. More rigorous T cell depletion of ATXBM, TCD host mice by infusion of antithymocyte globulin did not prevent delayed rejection of B6D2F1 skin initiated by transfer of Leu-Leu-OMe-treated B6 SpC. Despite the lack of complete prevention of skin allograft rejection, Leu-Leu-OMe treatment of B6 donor cells prevented lethal GVHD even in thymectomized B6D2F1 recipients. Precursors of anti-B6D2F1-specific CTL were greatly reduced or undetectable in unreconstituted ATXBM, TCD mice or in irradiated B6D2F1 recipients of Leu-Leu-OMe-treated B6 SpC. By contrast, ATXBM, TCD recipients of Leu-Leu-OMe-treated B6 SpC were found to contain a population of anti-class I MHC-specific CTL precursors of host origin within 28 days of reconstitution. These findings have indicated a number of features of the cells involved in skin graft rejection. First, Leu-Leu-OMe-sensitive CTL play a major role in acute rejection of class I + II MHC and multiple non-MHC antigen-disparate skin grafts. Moreover, the thymus-independent expansion of host-derived CTL precursors in ATXBM, TCD mice reconstituted with syngeneic Leu-Leu-OMe-resistant T helper cells also appears to play a role in mediating rejection of allogeneic skin grafts.
 ...
PMID:The role of leucyl-leucine methyl ester-sensitive cytotoxic cells in skin allograft rejection. 160 89

In a study designed to determine which T-cell subsets are involved in the development of murine graft-versus-host disease (GVHD), a prospective histologic analysis of gastrointestinal involvement was performed. In C57BL/6JXDBA/2F1 (B6D2F1) recipients of DBA/2 donor spleen and bone marrow cells, the colonic histologic findings were found to be similar in many respects to the histologic findings reported in human colonic GVHD and were much more severe and diffuse than were the abnormalities of the small intestine. Host irradiation before transplantation was found to play an additive or synergistic role in the development of GVHD. Furthermore the histologic features noted in DBA/2----B6D2F1 murine colonic GVHD suggest that bone marrow and spleen cell transplantation in this strain combination may be a useful model for studying the immunologic mechanisms involved in human inflammatory bowel disease. Thus severe colonic disease noted during the course of DBA/2----B6D2F1 murine GVHD was found to have significant histopathologic similarities to both human GVHD enteropathy and other inflammatory diseases of the human colon.
 ...
PMID:Histologic similarity of murine colonic graft-versus-host disease (GVHD) to human colonic GVHD and inflammatory bowel disease. 224 Jan 58