Correspondence

Turnover of Epidermal Langerhans' Cells

N Engl J Med 2004; 351:2661-2662December 16, 2004

Article

To the Editor:

Langerhans' cells are epidermal dendritic, antigen-presenting cells. Data from experiments in animals and observations in humans after transplantation of sex-mismatched bone marrow allografts have shown that Langerhans' cells originate from bone marrow precursors.1 However, epidermal Langerhans' cells are capable of self-regeneration, as shown by the incorporation of [³H]thymidine or bromodeoxyuridine2 and by electron-microscopical observations of mitotic Langerhans' cells.3 Recent data from studies in chimeric mice suggest that, under steady-state conditions, the efflux of Langerhans' cells to local lymph nodes would be balanced by the division of Langerhans' cells within the epidermis, whereas under conditions that severely deplete epidermal Langerhans' cells, keratinocyte-produced chemokines would recruit Langerhans'-cell precursors from the peripheral blood.4

So far, little is known about the kinetics of human epidermal Langerhans' cells under steady-state conditions. We report our observations concerning the presence of epidermal Langerhans' cells in the first double human hand allograft (transplantation was performed in January 2000).5 The recipient (but not the donor) was positive for HLA-A24. Twenty-four punch-biopsy specimens were taken from the skin of the allografts from day 0 to 4.5 years after transplantation. Tissue sections were immunolabeled with antibodies that recognize Langerhans' cells (CD207 [Langerin], CD1a, and S100 protein). Cells of recipient origin within the allograft were detected by immunolabeling with an antibody to the recipient's specific HLA-A24 antigen. Langerhans' cells were detected within the epidermis in all biopsy specimens of the allograft skin. Their number, distribution, and morphologic features appeared normal (Figure 1AFigure 1Immunostaining for Langerhans' Cells in the Skin of the Allograft (Immunoperoxidase with Aminoethylcarbazole).). The anti–HLA-24 antibody labeled cells of the recipient's own skin; by contrast, no reactivity was detected in the epidermis of the allografts at any time after transplantation, although occasional lymphoid HLA-A24–positive cells were present in the dermis (Figure 1B).

These results, showing that the Langerhans' cells present in the skin of the allografts remained of donor origin over a 4.5-year period, strongly suggest that, under steady-state conditions, the replacement of human epidermal Langerhans' cells by cells of bone marrow origin occurs at a very slow rate, if at all. In this patient, epidermal Langerhans' cells of the allograft may have persisted unchanged during the study period or may have been partly renewed from Langerhans'-cell precursors in the allograft. We conclude that in humans, as in mice,4 the replacement of epidermal Langerhans' cells by cells from bone marrow progenitors under steady-state conditions is very slow. A longer follow-up of this patient (or of other recipients of composite-tissue allografts containing skin) will show whether, under the influence of danger signals, some or all of the epidermal population of Langerhans' cells in the allograft will be replaced by cells that originate in the recipient's bone marrow.

Jean Kanitakis, M.D.
Palmina Petruzzo, M.D.
Jean-Michel Dubernard, M.D.
Edouard Herriot Hospital, 69437 Lyons, France

5 References

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Citing Articles (17)

Citing Articles

1. 1

   Chad R. Gordon, Fatih Zor, Maria Siemionow. (2011) Skin Area Quantification in Preparation for Concomitant Upper Extremity and Face Transplantation: A Cadaver Study and Literature Review. Transplantation 91:9, 1050-1056
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2. 2

   Jean Kanitakis, Emmanuel Morelon, Palmina Petruzzo, Lionel Badet, Jean-Michel Dubernard. (2011) Self-renewal capacity of human epidermal Langerhans cells: observations made on a composite tissue allograft. Experimental Dermatology 20:2, 145-146
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3. 3

   Laurent Chorro, Frédéric Geissmann. (2010) Development and homeostasis of ‘resident’ myeloid cells: the case of the Langerhans cell. Trends in Immunology 31:12, 438-445
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4. 4

   Florent Ginhoux, Miriam Merad. (2010) Ontogeny and homeostasis of Langerhans cells. Immunology and Cell Biology 88:4, 387-392
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5. 5

   Nikolaus Romani, Björn E. Clausen, Patrizia Stoitzner. (2010) Langerhans cells and more: langerin-expressing dendritic cell subsets in the skin. Immunological Reviews 234:1, 120-141
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6. 6

   Julie Helft, Florent Ginhoux, Milena Bogunovic, Miriam Merad. (2010) Origin and functional heterogeneity of non-lymphoid tissue dendritic cells in mice. Immunological Reviews 234:1, 55-75
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7. 7

   Maria Siemionow, Aleksandra Klimczak. (2010) Advances in the development of experimental composite tissue transplantation models. Transplant International 23:1, 2-13
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8. 8

   L. Chorro, A. Sarde, M. Li, K. J. Woollard, P. Chambon, B. Malissen, A. Kissenpfennig, J.-B. Barbaroux, R. Groves, F. Geissmann. (2009) Langerhans cell (LC) proliferation mediates neonatal development, homeostasis, and inflammation-associated expansion of the epidermal LC network. Journal of Experimental Medicine 206:13, 3089-3100
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9. 9

   Keiichi Muramatsu, Ryutaro Kuriyama, Toshihiko Taguchi. (2009) Intragraft Chimerism Following Composite Tissue Allograft. Journal of Surgical Research 157:1, 129-135
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10. 10

    M. Merad, M. G. Manz. (2009) Dendritic cell homeostasis. Blood 113:15, 3418-3427
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11. 11

    Maria Siemionow, Aleksandra Klimczak. (2009) Tolerance and Future Directions for Composite Tissue Allograft Transplants: Part II. Plastic and Reconstructive Surgery 123:1, 7e-17e
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12. 12

    Miriam Merad, Florent Ginhoux, Matthew Collin. (2008) Origin, homeostasis and function of Langerhans cells and other langerin-expressing dendritic cells. Nature Reviews Immunology 8:12, 935-947
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13. 13

    Keiichi Muramatsu, Ryutaro Kuriyama, Toshihiko Taguchi. (2008) Repopulation of donor cells from the recipient following extremity graft: Studies using the LACZ transgenic rat. Microsurgery 28:4, 279-284
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14. 14

    Wensheng Chen, Koji Hara, Qing Tian, Kanxing Zhao, Takeshi Yoshitomi. (2007) Existence of small slow-cycling Langerhans cells in the limbal basal epithelium that express ABCG2. Experimental Eye Research 84:4, 626-634
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15. 15

    G. Girolomoni, G. Zambruno, J. Kanitakis. (2007) C??lulas inmunocompetentes. EMC - Dermatolog??a 41:2, 1-11
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16. 16

    O. Thaunat, L. Badet, A. El-Jaafari, J. Kanitakis, J.-M. Dubernard, E. Morelon. (2006) Composite Tissue Allograft Extends a Helping Hand to Transplant Immunologists. American Journal of Transplantation 6:10, 2238-2242
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17. 17

    Siamon Gordon, Philip R. Taylor. (2005) Monocyte and macrophage heterogeneity. Nature Reviews Immunology 5:12, 953-964
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