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DOI: 10.1055/s-0028-1088232
Immunologic Responses in Vascularized and Nonvascularized Skin Allografts
Publication History
Publication Date:
16 September 2008 (online)
ABSTRACT
The skin is a protective interface between internal organs and the environment; it is the largest tissue of the human body. However, the skin does not serve merely as a physical barrier. It is also an active immune organ, traversed by a network of lymphatic and blood vessels. This immunologic structure contains immunologic cells such as T lymphocytes, Langerhans cells (LCs), dendritic cells, and keratinocytes. Langerhans cells represent the cutaneous counterpart of dendritic cells. LCs not only act as professional antigen-presenting cells to induce antigen-specific T cells for adaptive immune responses, but they also initiate a cascade of innate immune responses by antigenic stimulus such as transplant tissue. In transplantation immunology, either donor or recipient LCs fulfill an important mission in rejection or acceptance of donor tissue. Vascularized or nonvascularized skin allografts may create an immunologic response through different pathways. In both transplant models, skin diameter may change antigenic load, thereby determining rejection or acceptance response. This article discusses the effects of the cellular component in the skin immune system on immunologic responses of vascularized or nonvascularized skin allografts and describes the differences between the two immunologic cascades.
KEYWORDS
Skin allografts - vascularized skin allografts - skin immune system - transplantation immunology
REFERENCES
-
1 Streilein J W.
Skin-associated lymphoid tissue . In: Norris DA Immune Mechanisms of Cutaneous Disease. New York, NY; Marcel Dekker 1989: 73-95 - 2 Salmon J K, Armstrong C A, Ansel J C. The skin as an immune organ. West J Med. 1994; 160 146-152
- 3 Kupper T S. The activated keratinocyte: a model for inducible cytokine production by non-bone marrow-derived cells in cutaneous inflammatory and immune responses. J Invest Dermatol. 1990; 94 146S-150S
- 4 Hedger M P, Phillips D J, de Kretser D M. Divergent cell-specific effects of activin-A on thymocyte proliferation stimulated by phytohemagglutinin, and interleukin 1beta or interleukin 6 in vitro. Cytokine. 2000; 12 595-602
- 5 Tigelaar R E, Lewis J M, Bergstresser P R. TCR gamma/delta + dendritic epidermal T cells as constituents of skin-associated lymphoid tissue. J Invest Dermatol. 1990; 94 58S-63S
- 6 Bergstresser P R, Cruz Jr P D, Takashima A. Dendritic epidermal T cells: lessons from mice for humans. J Invest Dermatol. 1993; 100 80S-83S
- 7 Bos J D, Zonneveld I, Das P K, Krieg S R, van der Loos C M, Kapsenberg M L. The skin immune system (SIS): distribution and immunophenotype of lymphocyte subpopulations in normal human skin. J Invest Dermatol. 1987; 88 569-573
- 8 Rodeck U, Melber K, Kath R et al.. Constitutive expression of multiple growth factor genes by melanoma cells but not normal melanocytes. J Invest Dermatol. 1991; 97 20-26
- 9 Waelti E R, Inaebnit S P, Rast H P et al.. Co-culture of human keratinocytes on post-mitotic human dermal fibroblast feeder cells: production of large amounts of interleukin 6. J Invest Dermatol. 1992; 98 805-808
- 10 Marshall J S, Bienenstock J. The role of mast cells in inflammatory reactions of the airways, skin and intestine. Curr Opin Immunol. 1994; 6 853-859
- 11 Garside P, Mowat A M. Polarization of Th-cell responses: a phylogenetic consequence of nonspecific immune defence?. Immunol Today. 1995; 16 220-223
- 12 Springer T A. Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell. 1994; 76 301-314
- 13 Hilliges M, Wang L, Johansson O. Ultrastructural evidence for nerve fibers within all vital layers of the human epidermis. J Invest Dermatol. 1995; 104 134-137
- 14 Ansel J C, Brown J R, Payan D G, Brown M A. Substance P selectively activates TNF-alpha gene expression in murine mast cells. J Immunol. 1993; 150 4478-4485
- 15 Hosoi J, Murphy G F, Egan C L et al.. Regulation of Langerhans cell function by nerves containing calcitonin gene-related peptide. Nature. 1993; 363 159-163
- 16 Murray J E. Organ transplantation (skin, kidney, heart) and the plastic surgeon. Plast Reconstr Surg. 1971; 47 425-431
- 17 Lee W P, Yaremchuk M J, Pan Y C et al.. Relative antigenicity of vascularized limb allograft. Plast Reconstr Surg. 1991; 87 401-411
- 18 Mathes D W, Randolph M A, Solari M G et al.. Split tolerance to a composite tissue allograft in a swine model. Transplantation. 2003; 75 25-31
- 19 Hettiaratchy S, Melendy E, Randolph M A et al.. Tolerance to composite tissue allografts across a major histocompatibility barrier in miniature swine. Transplantation. 2004; 77 514-521
- 20 Lechler R, Ng W F, Steinman R M. Dendritic cells in transplantation: friend or foe?. Immunity. 2001; 14 357-368
- 21 Shortman K, Liu Y J. Mouse and human dendritic cell subtypes. Nat Rev Immunol. 2002; 2 151-161
- 22 Holt P G, Haining S, Nelson D J, Sedgwick J D. Origin and steady-state turnover of class II MHC-bearing dendritic cells in the epithelium of the conducting airways. J Immunol. 1994; 153 256-261
- 23 Stoitzner P, Holzmann S, McLellan A D et al.. Visualization and characterization of migratory Langerhans cells in murine skin and lymph nodes by antibodies against Langerin/CD207. J Invest Dermatol. 2003; 120 266-274
- 24 Medzhitov R. Toll-like receptors and innate immunity. Nat Rev Immunol. 2001; 1 135-145
- 25 Pierre P, Turley S J, Gatti E et al.. Developmental regulation of MHC class II transport in mouse dendritic cells. Nature. 1997; 388 787-792
-
26 Delves P J, Martin S J, Burton D R, Roitt I M.
Transplantation . In: Delves PJ, Martin SJ, Burton DR, Roitt IM Roitt's Essential Immunology. Malden, MA; Blackwell Publishing 2006: 364-380 - 27 Auchincloss Jr H, Sultan H. Antigen processing and presentation in transplantation. Curr Opin Immunol. 1996; 8 681-687
- 28 Grusby M J, Auchincloss Jr H, Lee R et al.. Mice lacking major histocompatibility complex class I and class II molecules. Proc Natl Acad Sci U S A. 1993; 90 3913-3917
- 29 Chen H D, Silvers W K. Influence of Langerhans cells on the survival of H-Y incompatible skin grafts in rats. J Invest Dermatol. 1983; 81 20-23
- 30 Brown J, Winklemann R K, Wolff K. Langerhans cells in vitiligo: a qualitative study. J Invest Dermatol. 1967; 49 386-390
- 31 Chih-chun Y, Tsi-siang S, Wei-shia X. A Chinese concept of treatment of extensive third-degree burns. Plast Reconstr Surg. 1982; 70 238-254
- 32 Alsbjorn B F, Sorensen B. Grafting of burns with widely meshed autograft split skin and Langerhans cell-depressed allograft split skin overlay. Ann Plast Surg. 1986; 17 480-484
- 33 Welsh E A, Kripke M L. Murine Thy-1 + dendritic epidermal cells induce immunologic tolerance in vivo. J Immunol. 1990; 144 883-891
- 34 Head J R, Billingham R E. Immunologically privileged sites in transplantation immunology and oncology. Perspect Biol Med. 1985; 29 115-131
- 35 Ito T, Ito N, Saathoff M et al.. Immunology of the human nail apparatus: the nail matrix is a site of relative immune privilege. J Invest Dermatol. 2005; 125 1139-1148
- 36 Billingham R E. Transplantation immunity evoked by skin homografts and expressed in intact skin. Adv Biol Skin. 1971; 11 183-198
- 37 Moseley R P, Brown J I, Auld J et al.. An immunocytochemical study of MHC class I expression on human Langerhans cells and melanocytes. J Pathol. 1997; 181 419-425
- 38 Slominski A, Wortsman J, Luger T, Paus R, Solomon S. Corticotropin releasing hormone and proopiomelanocortin involvement in the cutaneous response to stress. Physiol Rev. 2000; 80 979-1020
- 39 Stenn K S, Paus R. Controls of hair follicle cycling. Physiol Rev. 2001; 81 449-494
- 40 Niederkorn J Y. Mechanisms of immune privilege in the eye and hair follicle. J Investig Dermatol Symp Proc. 2003; 8 168-172
- 41 Paus R, Ito N, Takigawa M, Ito T. The hair follicle and immune privilege. J Investig Dermatol Symp Proc. 2003; 8 188-194
- 42 Chen H D, Silvers W K. Studies on the behavior of H-Y incompatible skin grafts in rats. J Immunol. 1982; 128 2044-2048
- 43 Nasir S, Krokowicz L, Bozkurt M, Siemionow M. Inlay technique for large skin graft replacement in the small animal. Plast Reconstr Surg. 2008; , In press
- 44 Strauch B, Murray D E. Transfer of composite graft with immediate suture anastomosis of its vascular pedicle measuring less than 1 mm. in external diameter using microsurgical techniques. Plast Reconstr Surg. 1967; 40 325-329
- 45 Ulusal B G, Ulusal A E, Ozmen S, Zins J E, Siemionow M Z. A new composite facial and scalp transplantation model in rats. Plast Reconstr Surg. 2003; 112 1302-1311
- 46 Demir Y, Ozmen S, Klimczak A, Mukherjee A L, Siemionow M. Tolerance induction in composite facial allograft transplantation in the rat model. Plast Reconstr Surg. 2004; 114 1790-1801
- 47 Nasir S, Sonmez E, Bozkurt M, Siemionow M. Extended groin flap model to increase antigenic load in immunological studies. Presented at: 2007 ASRM Annual Meeting January 2007 Rio Grande, Puerto Rico;
- 48 Selvaggi G, Levi D M, Kato T et al.. Expanded use of transplantation techniques: abdominal wall transplantation and intestinal autotransplantation. Transplant Proc. 2004; 36 1561-1563
- 49 Nasir S, Bozkurt M, Klimczak A, Siemionow M. Large antigenic skin load in total abdominal wall transplants permits chimerism induction. Ann Plast Surg. 2008; , In press
- 50 Valladeau J, Saeland S. Cutaneous dendritic cells. Semin Immunol. 2005; 17 273-283
- 51 Nasir S, Bozkurt M, Krokowicz L, Klimczak A, Siemionow M. Evaluation of immunologic differences in vascularized and non-vascularized skin allografts. Ann Plast Surg. 2008; , In press
- 52 Larsen C P, Steinman R M, Witmer-Pack M, Hankins D F, Morris P J, Austyn J M. Migration and maturation of Langerhans cells in skin transplants and explants. J Exp Med. 1990; 172 1483-1493
- 53 Monaco A P, Wood M L. Studies on heterologous antilymphocyte serum in mice. VII. Optimal cellular antigen for induction of immunologic tolerance with antilymphocyte serum. Transplant Proc. 1970; 2 489-496
- 54 Foster R D, Ascher N L, McCalmont T H, Neipp M, Anthony J P, Mathes S J. Mixed allogeneic chimerism as a reliable model for composite tissue allograft tolerance induction across major and minor histocompatibility barriers. Transplantation. 2001; 72 791-797
- 55 Hewitt C W, Black K S, Henson L E, Achauer B M, Nguyen J H. Lymphocyte chimerism in a full allogeneic composite tissue (rat-limb) allograft model prolonged with cyclosporine. Transplant Proc. 1988; 20 272-278
- 56 Lee W P, Rubin J P, Bourget J L et al.. Tolerance to limb tissue allografts between swine matched for major histocompatibility complex antigens. Plast Reconstr Surg. 2001; 107 1482-1490
- 57 Bourget J L, Mathes D W, Nielsen G P et al.. Tolerance to musculoskeletal allografts with transient lymphocyte chimerism in miniature swine. Transplantation. 2001; 71 851-856
Maria SiemionowM.D. Ph.D. D.Sc.
Department of Plastic Surgery, The Cleveland Clinic
9500 Euclid Avenue, Desk A-60, Cleveland, OH 44195
Email: siemiom@ccf.org