Turnover of Epidermal Langerhans' Cells
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《新英格兰医药杂志》
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 1A). 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).
Figure 1. Immunostaining for Langerhans' Cells in the Skin of the Allograft (Immunoperoxidase with Aminoethylcarbazole).
Panel A shows Langerhans' cells detected in the epidermis of the allograft 4.5 years after transplantation. In Panel B, the anti–HLA-24 antibody reveals some lymphoid HLA-A24–positive cells of recipient origin in the dermis of the allograft. No reactivity is evident within the epidermis.
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
References
Schmitt D. Découverte et histoire de la cellule de Langerhans. In: Schmitt D, ed. La cellule de Langerhans humaine. Paris: INSERM, 2003:1-28.
Czernielewski JM, Demarchez M. Further evidence for the self-reproducing capacity of Langerhans cells in human skin. J Invest Dermatol 1987;88:17-20.
Kanitakis J, Hoyo E, Perrin C, Schmitt D. Electron-microscopic observation of a human epidermal Langerhans cell in mitosis. J Dermatol 1993;20:35-39.
Merad M, Manz MG, Karsunsky H, et al. Langerhans cells renew in the skin throughout life under steady-state conditions. Nat Immunol 2002;3:1135-1141.
Petruzzo P, Revillard JP, Kanitakis J, et al. First human double hand transplantation: efficacy of a conventional immunosuppressive protocol. Clin Transplant 2003;17:455-460.
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 1A). 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).
Figure 1. Immunostaining for Langerhans' Cells in the Skin of the Allograft (Immunoperoxidase with Aminoethylcarbazole).
Panel A shows Langerhans' cells detected in the epidermis of the allograft 4.5 years after transplantation. In Panel B, the anti–HLA-24 antibody reveals some lymphoid HLA-A24–positive cells of recipient origin in the dermis of the allograft. No reactivity is evident within the epidermis.
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
References
Schmitt D. Découverte et histoire de la cellule de Langerhans. In: Schmitt D, ed. La cellule de Langerhans humaine. Paris: INSERM, 2003:1-28.
Czernielewski JM, Demarchez M. Further evidence for the self-reproducing capacity of Langerhans cells in human skin. J Invest Dermatol 1987;88:17-20.
Kanitakis J, Hoyo E, Perrin C, Schmitt D. Electron-microscopic observation of a human epidermal Langerhans cell in mitosis. J Dermatol 1993;20:35-39.
Merad M, Manz MG, Karsunsky H, et al. Langerhans cells renew in the skin throughout life under steady-state conditions. Nat Immunol 2002;3:1135-1141.
Petruzzo P, Revillard JP, Kanitakis J, et al. First human double hand transplantation: efficacy of a conventional immunosuppressive protocol. Clin Transplant 2003;17:455-460.