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1.
Transplant Proc ; 42(9): 3347-53, 2010 Nov.
Article in English | MEDLINE | ID: mdl-21094778

ABSTRACT

The immunosuppressive medications developed over the past 3 decades have paved the way for solid organ transplantation to become the treatment of choice for end-stage organ failure. At the end of the century, composite tissue transplantation in humans was performed with success using the same immunosuppressive medications and therapeutic principles. A decade later, experience from >100 cases of reconstructive transplantation have increased the knowledge, changed the view, and affected the therapeutic principles in this novel field. We herein portray the evolution of this novel type of transplant with particular reference to immunologic aspects, particularly differences between reconstructive and solid organ transplantation.


Subject(s)
Graft Rejection/prevention & control , Graft Survival/drug effects , Immunosuppressive Agents/therapeutic use , Organ Transplantation , Tissue Transplantation , Animals , Graft Rejection/immunology , Humans , Organ Transplantation/adverse effects , Time Factors , Tissue Transplantation/adverse effects , Transplantation, Homologous , Treatment Outcome
2.
Am J Transplant ; 10(5): 1200-9, 2010 May.
Article in English | MEDLINE | ID: mdl-20353468

ABSTRACT

Skin rejection remains a major hurdle in reconstructive transplantation. We investigated molecular markers of skin rejection with particular attention to lymphocyte trafficking. Skin biopsies (n = 174) from five human hand transplant recipients were analyzed for rejection, characteristics of the infiltrate and lymphocytic adhesion markers. The cellular infiltrate predominantly comprised CD3+ T cells. CD68, Foxp3 and indoleamine 2, 3-dioxygenase expression and the CD4/CD8 increased with severity of rejection. Lymphocyte adhesion markers were upregulated upon rejection, intercellular adhesion molecule-1 and E-selectin correlated best with severity of rejection. Guided by the findings, a specific E- and P-selectin inhibitor was investigated for its effect on skin rejection in a rat hind limb allotransplant model. While efomycine M (weekly s.c. injection into the graft) alone had no effect, long-term allograft survival was achieved when combined with antithymocyte globulin and tacrolimus (control group without efomycine M rejected at postoperative day [POD] 61 +/- 1). Upregulation of lymphocyte trafficking markers correlates with severity of skin rejection and time after transplantation in human hand transplantation. Blocking E- and P-selectin in the skin holds potential to significantly prolong limb allograft survival.


Subject(s)
E-Selectin/immunology , Intercellular Adhesion Molecule-1/immunology , P-Selectin/immunology , Animals , Antigens, CD , Antigens, Differentiation, Myelomonocytic , Antilymphocyte Serum/immunology , Biomarkers , Biopsy , Humans , Lymphocytes/immunology , Lymphocytes/pathology , Male , Rats , Rats, Inbred BN , Rats, Inbred Lew , Skin/immunology , Skin/pathology , Tacrolimus/immunology , Time Factors
3.
Transplant Proc ; 41(2): 509-12, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19328914

ABSTRACT

Human hand transplantation is complicated by skin rejection. To better define the characteristics of infiltrating cells, biopsies from human hand transplants have been investigated for expression of Foxp3 and indoleamine 2,3-dioxygenase (IDO), a key regulatory enzyme to induce T-lymphocyte unresponsiveness. A total of 104 skin biopsies taken from three bilateral hand transplant recipients over 6 years posttransplant were assessed by hematoxylin-eosin histology (graded 1-4b) and immunohistochemistry for IDO and Foxp3 according to a three-grade classification and correlated with the grade of rejection as well as time after transplantation. Overall, rejection ranged between grades 0 and 4a with an average score of 0.94. IDO was expressed in the endothelium independent of rejection. Upon rejection, IDO staining within the cellular infiltrate was significantly increased. Foxp3 in regulatory T cells was mainly found in samples undergoing severe rejection. Expression of IDO and Foxp3 compared well to each other, although the overall expression of Foxp3 was lower when compared to IDO. An increased expression of IDO as well as Foxp3 during rejection late after transplantation was observed. Characteristics of the cellular infiltrate indicate tolerogenic properties of a proportion of the cells and therefore a tendency toward self-limitation of the alloimmune response during skin rejection after hand transplantation.


Subject(s)
Forkhead Transcription Factors/metabolism , Hand Transplantation , Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism , Skin Transplantation/pathology , Biomarkers/metabolism , Graft Rejection/immunology , Humans , Immunohistochemistry , Immunosuppressive Agents/therapeutic use , T-Lymphocytes, Regulatory/immunology , Transplantation, Homologous/immunology , Transplantation, Homologous/pathology
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